Diabetes - diagnosis,complication and monitoring by Dr Prabhash

Click here to load reader

Embed Size (px)

description

pathophysiology of diabetes and its complications. monitoring of diabetes, newer modalities for assessing blood glucose

Transcript of Diabetes - diagnosis,complication and monitoring by Dr Prabhash

  • 1. Diabetes Mellitus Dr. Prabhash Bhavsar

2. Blood Glucose Regulation 3. Diabetes is a group of Metabolic Disorders characterized by Hyperglycemia resulting from defects in insulin secretion, insulin action, or both. -Diabetes Care Volume 37, Supplement 1, January 2014, S81 4. Etiological Classification of DM iType 1 DiabetesImmune mediated cell destruction, idiopathiciiType 2 DiabetesInsulin resistanceiiiGenetic defect of cell functionMODYGenetic defect in insulin processing Defect in proinsulin conversion, insulinor action gene & receptor mutation etc. Exocrine pancreatic defect Other endocrinopathiesGlucagonoma, hyperthyroidism, cushing syndrome etc.infectionsCMV, Coxsackie B etc.DrugsSteroids, thyroxin, adrenergic etc.Genetic syndromes ivPancreatitis, cystic fibrosis etc.Down, turner etc.Gestational Diabetes Mellitus Diabetic care 25, 2003 5. Pathogenesis of type1 DM Genetic susceptibilityEnvironmental triggerAutoimmunity cell destruction 6. Genetics Susceptibility of type1 DM is inherited. Mode of inheritance is complex. Concordance rate between identical twins is 30%. MHC on chromosome 6 Multigenic trait INS gene on chr 11 other loci on chr 9 HLA DQ & DR are most important determinant. HLA DQB1*0602 allele significantly reduces the risk of type1 DM. INS VNTR also increases the risk. Routine assessment of genetic markers is not recommended for x and Mx. 7. Environmental factors Viruses such as rubella, mumps and coxsackie B have been implicated. Autoimmunity to cell is initiated by viral proteins. Genetic susceptibility determines the progression of cell destruction. 8. Autoimmunity Type1 DM results from cell mediated autoimmune destruction of pancreatic cell. 80-90% destruction of cell is required to induce symptomatic diabetes. Marker of cell autoimmunity are circulating antibodies. They are present in the serum years before the onset of hyperglycemia. 9. -Islet cell cytoplasmic antibodies (ICAs): Against sialoglycoconjugate antigen present in the cytoplasm of all endocrine cells of the pancreatic islets. Detectable in 75-80% of newly diagnosed DM type1 and 0.5% of normal subjects. Insulin autoantibody: detectable in >90% of type1 DM developing before age 5. 50% of newly diagnosed type1 DM. Zinc transporter (ZnT8): - It is recently identified major autoantigen in type1 DM - 60-80% of type1DM, 150 and HDL 0.9 M & >0.85 F or BMI >30Insulin resistanceurinary albumin excretion 20 g/min or albumin : creatinine ratio 30 mg/g 19. Type1Normal or increased No (if +ve LADA)Ketoacidosis is commonHyperosmolar state common30% concordance in twins~100%HLA linkedNot linkedAutoimmunityInsulin resistanceSevere insulin deficiency Islet cell histologyObese mostlyAutoantibodies +vepathogenesis>30 years blood insulin levelsGeneticsOnset < 20 year Normal or underweightClinicalType2Relative insulin deficiencyInsulitisNOMarked atrophy and fibrosisFocal atrophy with amyloidosisSevere beta cell depletionMild beta cell depletion Dr. Prabhash 20. Complications of Diabetes Mellitus 21. Effect of insulin on metabolism Carbohydrate metabolism: - glucose uptake in muscle and adipose tissues - In liver : glycogenesis glycogenolysis & gluconeogenesis Fat metabolism: - TG degradation by inhibiting lipoprotein lipase - TAG synthesis in adipose tissues. Protein metabolism: - AA entry into the cells - protein synthesis by activating translational factors 22. Meal absorbed Plasma glucosePlasma fatty acidPlasma amino acidNo insulin released Fat breakdownFat storagePlasma fatty acidGlucose uptakeGlucose utilizationAminoacid uptakePlasma amino acidLiver Ketones glycogenolysis gluconeogenesisTissue lossBrain interpret as starvationventilationMetabolic acidosisProtein breakdownTissue losshyperglycemia polyphagiaOsmotic diuresis Lactic acidosis Anaerobic metabolismthirst Coma and deathdehydration Hypovolemia & Hypotension Circulatory failurepolydipsia 23. Long term complications 24. Diagnostic criteria for DM Any one of the following is diagnostic A. Glucose 1. Fasting plasma glucose 126 mg% or 2. Symptoms of hyperglycemia and casual plasma glucose 200mg% or 3. During an OGTT 2 hour plasma glucose 200mg% B.HbA1c 6.5 mg%Point of care assay should not be used for diagnosis. 25. Pre clinical screening of DM Type1 DM:-Screening is not recommended other than clinical studies.-Islet cell autoantibody detection may be useful in- (1) identifying LADA (2) to screen non diabetic family member who wish to donate kidney or part of pancreas fir transplantation (3) screening of women with GDM to identify those at high risk of progression to type1 DM(4) distinguishing type1 from type2 in children to institute insulin at the time of diagnosis.-HLA typing is not recommended.-Glucose induced insulin secretion test is also not recommended for routine clinical use. 26. Type 2 DM-All asymptomatic individuals over 45 years of age-Overweight children with any of the two following risk factors- (i) type2 DM in of 1st or 2nd degree relative (ii) high risk race/ethnic group (iii) have conditions associated with insulin resistance (iv) maternal history of GDM. Testing should be done every 3 years starting at the age of 10.-Screening can be done using fasting glucose, 2 hour OGTT or HbA1c. 27. Monitoring of blood glucose SMBG:-With glucometer-Indications (1) patient under intense insulin therapy- 4-5 times a day. (2) prevention and detection of hypoglycemia, especially in those who are not able to recognize the early warning signs. (3) avoidance of severe hyperglycemia especially when having medication that alter insulin secretion and action (4) adjusting the dose in response to life style modification, exercise, food taken etc. (5) determination of necessity for initiating insulin therapy in GDM-Should not be used for diagnosis. 28. Minimally invasive monitoring of blood glucose: Implanted sensors: - CGMS- needle type of sensor, monitors glucose 1 to 5 minute from interstitial tissue fluid.- Glucoday- microdialysis, every second Gluco watch biographer: - Low level electric current moves glucose across the skin by electroosmosis where measured by GOD 29. Noninvasive glucose monitoring Glucose has specific absorption at 1035nm - Near infrared spectroscopy - Raman scattering spectroscopy - Photoacoustic spectroscopy All under active investigation and considerable success has been achieved but none is FDA approved for clinical use. 30. Monitoring long term glucose control -Glycated hemoglobin Gives an idea of glucose control over past 3 months Goal is to keep it below 7%. Should be repeated every 6 months in patients meeting the treatment goal Estimated average glucose mg% = 28.7*HbA1c 46.7 Altered life span of RBCs affect the result significantly. Fructosamine Proteins (other than Hb) with nonenzymatic attachment of glucose are known as fructosamine. Reflect glucose control over past 2-3 weeks. Should not be done in patients with hypoalbuminemia. 31. others Microalbuminuria Evaluating complications- creat, lipid profile, ketone bodies, electrolytes, lactate etc. HOMA-IR = insulin (mU/L) * glucose (mg%) / 405 C-peptide assessment. 32. Thank you