LABORATORY SCREENING, DIAGNOSIS & MONITORING OF DIABETES MELLITUS R. Mohammadi Biochemist (Ph.D.) Faculty member of Medical Faculty

Transcription

1 LABORATORY SCREENING, DIAGNOSIS & MONITORING OF DIABETES MELLITUS R. Mohammadi Biochemist (Ph.D.) Faculty member of Medical Faculty

2 DIAGNOSTIC SENSITIVITY AND DIAGNOSTIC SPECIFICITY

3 Clinical Application of Tests Screening Test Confirmatory Tests Diagnostic Tests Monitoring i of Therapy Effectiveness Recurrence Prognosis

4

5

6 CLASSIFICATION OF PATIENTS ACCORDING TO TEST RESULTS Patients Are Four Groups: True Positive (TP) False Positive (FP) True Negative (TN) False Negative (FN)

7 Patient = TP + FN True Positive (TP) False Negative (FN) Nonpatient = TN + FP True Negative (TN) False Positive (FP)

8 192 Patient individuals 151 True Positive (TP) 41 False Negative (FN) 578 Nonpatient idividuals 265 True Negative (TN) 313 Positive (FP)

9 DIAGNOSTIC SENSITIVITY Is the Probability of Positive Test in Patients Affected by that Disease TP Sensitivity (%) = x 100 TP + FN % = x

10 DIAGNOSTIC SPECIFIVITY Is the Probability of Negative Test in Patients Unaffected by that Disease TN Specificity (%) = x 100 TN + FP 46% = x %

11 DIAGNOSTIC ACCURACY DEPENDS ON CUTOFFs

12 PREDCTIVE VALUE OF POSITIVE TEST the Probability of Individuals with Positive Test that Are Patient TP PV + = x 100 TP + FP 33% = x % = x

13 PREDCTIVE VALUE OF NEGATIVE TEST the Probability of Individuals with Negative Test that Are Nonpatient TN PV - = x 100 TN + FN 33% = x % = x

14 EFFICIENY OF TEST Is Probability of Correct Classification of Patients & Nonpatients on the Basis of the Test TP + TN Efficacy of Test (%) = x 100 TP + FN + TN + FP 54% = x % = x

15

16 Laboratory Tests in Screening, Confirmation, and Monitoring of Diabetes Mellitus Random Blood Glucose (BS) Fasting Blood Glucose (FBS) 2hpp, 4PM BS, 5PM BS Challenge and Tolerance Test HbA1C Ketone Bodies Microalbumin Insulin C Peptide Autoantobodies Other Specific Tests

17 DIAGNOSTIC TESTS Blood Sugar (BS)

18 DIAGNOSTIC TESTS Fasting Blood Sugar (FBS) Fasting Plasma Glucose (FPG) Fasting Serum Glucose (FSG) Normal <100 mg/dl Impaired Fasting Glucose (IFG) mg/dl Diabetes >125 mg/dl

19 DIAGNOSTIC TESTS Glucose Tolerance Test (GTT) 1) Oral GTT (O-GTT) 2) Intravenous GTT

20 Factors Affecting on GTT Carbohydrate Intake, Previous Food Intake, Hospitalization, Surgery, Immobility Gatrointestinal Abnormalities Stress, Smoking, Coffeine Drugs including OCP, Propranolol, Corticosteroids

21 O-GTT Procedure Giving 75 g Glucose in 300 ml Water to Adults and 1.75 g/kg to Children Glucose Solution Must Be Consumed within 5 Min Taking Blood in Fasting, 0.5, 1.0 and 2.0 Hours Later

22 تقسيمبندي مي شوند. اين ديابتي تقسيم و مختل طبيعي طبيع تحمل گروه سه به افراد حاصل نتايج اساس دارند. بر بين ناشتاي گلوكز مقادير كه ميشود انجام افرادي بر بر روي ازمون گلوكز. اين تحمل ازمون شكل ۳۹-۱۵ بيشتر براساس گلوكز ۲ ساعت ميباشد كه به ترتيب زير بين ۱۴۰ و و يا بيشتر قرار ميگيرد.

23 Diagnosis on the Basis of 2.0 h Serum Glucose Normal <140 mg/dl Impaired Glucose Tolerance mg/dl Diabetes >200 mg/dl

24 O-GTT for Diagnosis of GDM GTT with 50 g Glucose during Week <130 mg/dl Normal = > 130 mg/dl GTT 3h GTT with 100g and Serum Glucose in Fasting, 1, 2, 3 h Later FBS <105 mg/dl 1.0 h <190 mg/dl 2.0 < 165 mg/dl 3.0 h < 145 mg/dl At Least Two Abnormal Results GDM

25 DETECTION OF KETONE BODIES Including Acetoacetate, Acetone,, and β Hydroxybutyrateβ Ketonemia & Ketonuria Reflects Inappropriate Therapy In Fresh Serum or Urine

26 GLYCATED PROTEINS Glycated Hemoglobin Fructosamine

27 GLYCATED HEMOGLOBIN Binding to β Chain (HbA 1 ) HbA 1a1 Froctose 1,6-diphosphate HbA 1a2 Glucose 6-phosphate HbA 1b Pyruvate HbA 1C Glucose Binding to α Chain (HbA 0 )

28 HbA 1C FORMATION

29

30 MICROALBUMIN Microalbuminuria Is Presence of Albumin in urine above The Normal Level, But Blow The Detectable Range of Conventional Urine Dipstick Methods Microabluminuria Is defined as persistent albuminuria in the range of 30 to 299 mg/24h Macroabluminuria Is defined as persistent albuminuria i in the range of 300 mg/24 24h

31 MICROALBUMIN Microalbuminuria Is Considered As a Clinically Important Indicator of Deteriorating Renal Function in Diabetic Subjects Regular Screening of Microalbuminuria Is Valuable in Monitoring of Both Type 1 & Type 2 Diabetics i

32 MICROALBUMIN There Is No Consensus about How A Urine Sample Should Be Collected Urine Albumin Excretion Is Dependent on: 1) Urine Flow Rate 2) Exercise 3) )Posture

33 MICROALBUMIN Sample Should Not Be Collected: 1) In the Presence of Urinary Tract Infection 2) Immediately after Surgery 3) After Acute Fluid Load Because of High Intraindividual Variation & Diurnal Variation, at Least Three Separate Samples Should Be Collected within a 3 to 6 Month Period Microalbuminuria Is Present When 2 of 3 Specimens Are Abnormal.

34 MICROALBUMIN Suggested Urine Samples Are: Early Morning Urine Collection Upon awaking and prior to breakfast or exercise Determining albumin (μg/l) -creatinine (mg/l) ratio Normal : < 30 μg/mg Microalbuminuria : μg/mg g g Mcroalbuminuria : 300 μg/mg Timed Overnight Urine Collection ( h) Beginning from bedtime by discharging Urine Ending when bladder is emptied the next morning 24-h Urine Collections Is Not Suitable

35 MICROALBUMIN Urine Should Be Collected at 4 o C after Collection Adding Preservatives Is Not Necessary, But 2 ml Sodium Azide Can Be Used for 500 ml Urine Bacterial Contamination & and Glucose Has No Effect Specimens Are Stable for 2 wk at 4 o C and for 5 mo at -70 o C.

36 INSULIN Insulin measurments are not required for diagnosis of DM But can be used for 1) Determination insulin resistance 2) Diagnosis of insulinoma

37 CPeptide Is a marker for endogenous insulin production which can be used for Differentiation of type 1 and type 2 Diagnosis of insulinoma Detection of insulin injection

38 AUTOANTIBODIES Autoanibodies are seen in about 95% of DM type 1, So about 5% patients have no antibodies and absence of antibodies does not exclude diagnosis These antibodies are commomnly present before and at the time of onset of diabetes. Most common autoantibodies include GAD65, IAA, and ICA512 Diagnostic sensitivity is about 99%, but diagnostic specificity is lower. GAD65 has the highest sensitivity (91%) IAA is more common in young children, and CAD65 is more common in adults

39 AUTOANTIBODIES Autoantibodies are present during pre-diabetes period of gradual and progressive beta cell destruction which may last months, years, or decades These antibody assays are being used in type 1 diabetes detection, treatment, and prevention research At present their use for routine screening in asymptomatic individuals is not recommended. Presence of autoantibodies may help in differentiation of type 1 diabetes from other types od diabetes early in the course of fth the disease

40 OTHER SPECIFIC TESTS These are tests for evaluating conditions such as pancreatitis and endocrinopathies that result in hyperglycemia y

41