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by: drsushil7781

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1 : HbA1c to detect T2DM & Impaired Glucose Regulation Dr sushil
2 : Diabetes mellitus (DM) : “ Group of common metabolic disorders that share the phenotype of hyperglycemia ” Type 1 DM ? Insulin deficiency Type 2 DM ? Insulin resistance Impaired insulin secretion Increased glucose production
3 : Spectrum of glucose homeostasis & DM :
4 : Diagnosis : Diagnostic criteria based on 2 premises: FPG & response to an oral glucose load ? varies among normal individuals DM ? level of glycemia at which complications occur ( not on mean – deviations )
5 : Diagnosis withdrawn if FPG reverts to normal
6 : Impaired Glucose Regulation : Impaired Fasting Glucose (IFG) : 100–125 mg/dL Impaired Glucose Tolerance (IGT) : 140 -199 mg/dL IFG and/or IGT -- pre-diabetes Risk for developing type 2 DM : 25–40% risk over the next 5 years ?Risk of cardiovascular disease
7 : There is a call to change the Diagnostic criteria for Type 2 DM …….. WHY…??
8 : Average period between developing T2DM & subsequent diagnosis ? 7 yrs Macrovascular complications of hyperglycemia have developed in 20-30% Onset is preceded by latent phase of impaired glucose regulation IGT/IFG (Prediabetes)
9 : Chronic multisystem disease Debilitating macrovascular complications Reduce quality of life & Length of life by 10-15 yrs 10-15% of total healthcare budget Global obesity epidemic
10 : Screening for both IGR & T2DM ? More cost effective than T2DM alone
11 : Current Screening Tests Insufficient……… WHY ?? 3 reasons…..
12 : FPG /OGTT : Precise preparation required Glucose lowering interventions (3 days) Overnight fasting ( 8hrs) Stress – Affects result Samples placed on ice Processed within 1 hr (WHO ) Initial FPG/ OGTT -- Diabetic range ? Repeat test (3 days) to confirm
13 : Lower screening rates Sensitivity of FPG ? 40-60%
14 : Under diagnosis of T2DM FPG ? Pancreatic ß cell dysfunction Doesn’t assess post-prandial hyperglycemia (PPH) (Insulin resistance) FPG doesn’t detect PPH
15 : Glycated HbA1c
16 : Non enzymatic reversible glycation of N- terminal valine residues of Hb ? proportionately with ? glucose intolerence ABG for RBC lifespan (2-3 mths) Last month ? Contributes 50% Recent change in diet or treatment ? alters HbA1c values within 6 wks
17 : HbA1c - Current recommendations Monitoring progress of T2DM Guide to start treatment No clear role in diagnosis
18 : For detecting T2DM HbA1C equally good as FPG Potential Advantages of HBA1c: * Non-fasting state * Reflects long term glycemia * Less affected by recent sress * Contributions from both fasting & postprandial glucose
19 : * Higher reproducibility rate than FPG * Less intraindividual variation (2% Vs 12-15%) * Continuous relationship with cardiovascular events (even below T2DM diagnostic threshold)
20 : Role in Diagnosis – T2DM International Expert Committee in 2009 recommended -- HbA1c > 6.5% (48 mmol/mol) 2nd positive test required in asymptomatics HbA1c > 6.5% -- ? prevalence of retinopathy
21 : Role in Diagnosis - IGR HbA1c 6.0-6.4% -- International expert committee 5.7-6.4% -- ADA
22 : Reporting unit UKPDS/NGSP -- % IFCC -- mmol/mol Hb Conversion : % ? mmol/mol HbA1c = ( HbA1c - 2.15) ×10.929 (mmol/mol) (%)
23 : Substract 2, substract 2rule: Only for whole numbers 4 - 13% Value in % = x Then, y = x - 2 z = y – 2 Value in mmol/mol = yz
24 : Substract 2, substract 2rule: Example: Value in % (x) = 9 % Then, y = x– 2 = 9 - 2 = 7 z = y – 2 = 7 - 2 = 5 Value in mmol/mol = yz = 75 mmol/mol
25 : Routine values:
26 : HbA1c to estimate ABG: e ABG = (28.7 × HbA1c ) – 46.7 (mg/dl) (%) Example: HbA1c = 8% eABG = (28.7 × 8) - 46.7 = 182.9 mg/dl
27 : Limitations : More false positives More false negatives Useful only for normal Hb False results with abnormal Hb ( HbS, HbC, HbE) Not applicable to Type 1 DM Gestational DM Ethinic disparity (Higher HbA1c in blacks) Ethnic specific cut-points required
28 : Limitations : Falsely raised HbA1c -- ? RBC life span ( longer exposure time ) Causes: Uremia Hypertriglyceredaemia Hyperbilirubinemia Falsely Decreased HbA1c: -- ? RBC life span ( less exposure time) Causes: Blood loss Sickle cell anaemia Thalassaemia G6PD deficiency Splenectomy Hemolytic anaemia Aplastic anaemia
29 : Situations where HbA1c is unreliable ? Use Fructosamine test
30 : HbA1c for Diagnosis -- Double Edged Sword
31 : Increased Diagnosis -- Increased Prevalence (HbA1c >6.5% but normal glucose testing) Additional group Natural course Do not progress to of complications developing complications Early interventions Wastage of resources HbA1c –beneficial HbA1c harmful
32 : Potential Economic Impact HbA1C Less time consuming More expensive Fewer resourses than glucose testing
33 : How HbA1C Can be used for diagnosis?
34 : Using single cut-point -- HbA1c 6.5% More False Positives More False Negatives Use two cut-points— HbA1c <5.5% ? Rule - out diabetes HbA1c >7% ? Rule - in diabetes In between ? Use Glucose Testing
35 : Recent Trends -- POCT Portable Point of Contact machines Instant readings using finger prick Currently used for monitoring Not for diagnosis ( Suboptimal precision)
36 : Home message: HbA1c -- Will simplify screening of T2DM -- Approved by ADA, not by WHO -- Soon become an additional diagnostic criteria for T2DM -- Reduce gap between diagnosed & undiagnosed people
37 : THANK YOU…

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