hemoglobin a1c in the diagnosis and management of diabetes grand... · hemoglobin a1c in the...

Hemoglobin A1c in the Diagnosis and Management of

Diabetes

Separation Science

Non-enzymaticBiochemistry

DiabetesMonitoring

A1c AssayStandardization

DCCT UKPDS

Ignoring BiologicalVariation in A1c

1.1. Describe what clinical laboratories actually Describe what clinical laboratories actually measure as HbA1cmeasure as HbA1c

2.2. Show that HbA1c and mean blood glucose are Show that HbA1c and mean blood glucose are not interchangeable estimates of glycemic not interchangeable estimates of glycemic controlcontrol

3.3. Explain how biological variation in HbA1c Explain how biological variation in HbA1c complicates new guidelines for the diagnosis complicates new guidelines for the diagnosis and management of diabetesand management of diabetes

ObjectivesObjectives

Main Take-home Message

The quantitative relationship between

blood glucose concentration and

hemoglobin A1c is not the same in all people

MBG = A1c

MBG A1c

(A415 nm)

globins

→

+

Monomers

+

Dimers

↔

Tetramer

Higher Hemoglobin ConcentrationHigher pH

Oxygenation

Globin Association is DynamicMW 15258 15867 31125 62249

Order of affinity Val1 Lys66 Lys61 Lys17 Val1 Lys40 Lys8

Known Glucose Binding Sites

8

17

1

40

61

V--NHNH22 HC=OHC=O׀ ׀

HCOHHCOH׀ ׀

HOCH HOCH ׀ ׀

HCOHHCOH׀ ׀

HCOHHCOH׀ ׀

CHCH22OHOHGlucoseGlucose

++

globinglobin

Non-enzymatic Hb glycation

V--NHNH--CHCH22 ׀ ׀C=OC=O׀ ׀

HOCH HOCH ׀ ׀

HCOHHCOH׀ ׀

HCOHHCOH׀ ׀

CHCH22OHOHStable A1cStable A1c

(ketoamine/Amadori)(ketoamine/Amadori)

Slow 2

V --N=N=CHCH׀ ׀

HCOHHCOH׀ ׀

HOCH HOCH ׀ ׀

HCOHHCOH׀ ׀

HCOHHCOH׀ ׀

CHCH22OHOH

Labile A1cLabile A1c(aldimine/Schiff base)(aldimine/Schiff base)

Rapid 1

+ + HH22OO

MaillardMaillardReactionReaction

Role of lysine and -amino groups

HC=OHC=O׀ ׀

HCOHHCOH׀ ׀

HOCH HOCH ׀ ׀

HCOHHCOH׀ ׀

HCOHHCOH׀ ׀

CHCH22OHOHGlucoseGlucose

++

globinglobin

V--NHNH22

--NHNH22K

Slow 2

--NHNH--CHCH22 ׀ ׀C=OC=O׀ ׀

HOCH HOCH ׀ ׀

HCOHHCOH׀ ׀

HCOHHCOH׀ ׀

CHCH22OHOHAmadoriAmadori

V--NHNH22

K

Schiff baseSchiff base

CHCH׀ ׀

HCOHHCOH׀ ׀

HOCH HOCH ׀ ׀

HCOHHCOH׀ ׀

HCOHHCOH׀ ׀

CHCH22OHOH

N=N=

V--NHNH22

K

Rapid 1+ + HH22OO

1960 1970 1980 1990 2000 2010 20201950

Sickle

Kunkel HG, Wallenius G. New hemoglobin in normal adult blood. Science 122:288, 1955

Discovery of Hemoglobin Heterogeneity

Fast Hb

Morrison M, Cook JL. Chromatographic fractionation of normal adult oxyhemoglobin. Science 122:920-1,1955

Fast HbIRC-50 (Bio-Rex) cation exchange

Fast HbHemoglobin Heterogeneity

in Normal Blood

1960 1970 1980 1990 2000 2010 20201950Identification of Hemoglobin A1c

AI AII

Allen DW, Schroeder, W.A. and Balog, J. J Am Chem Soc 80:1628-34, 1958

IRC-50 (Bio-Rex) cation exchange

Morrison M, Cook JL. Chromatographic fractionation of normal adult oxyhemoglobin. Science 122:920-1,1955

Fast Hb

Fast HbSickle AIc


AI AII


AIc

Fast HbSickle

AIc

AIa

AIb

Hemoglobin AI HeterogeneityPeaks designated a, b, c in order of appearance


“The designations, AI, AII and others, are given for

convenience of reference in this discussion. It is not our purpose

to propose a system of nomenclature”


AIc

Fast HbSickle

AIc

AIa

AIb

Hemoglobin AI HeterogeneityPeaks designated a, b, c in order of appearance


AIc

Fast HbSickle

Clegg MD, Schroeder WA. J Am Chem Soc 1959;81:6065-9.

Additional heterogeneity of normal hemoglobin

Nomenclature Problem

1960 1970 1980 1990 2000 2010 20201950

Holmquist, W. R. & Schroeder, W. A. A new N-terminal blocking group involving a Schiff base in hemoglobin AIc. Biochemistry 5: 2489-2503, 1966

Chromatography of tryptic peptides

Paper electrophoresis of chromatography fractionsAIcT-1

Fraction 5 of hemoglobin AIc, but not AII, contained chemically modified N-terminal

beta globin peptides

Characterization of Hemoglobin A1c

AIc

Fast HbSickle

1960 1970 1980 1990 2000 2010 20201950

dimers

Globinchains

“The studies described in the present report indicate that a hexose is linked to the N-terminal of the AIc chain - the possible attachment of other structures to the hexose has not been excluded…”

- +

Bookchin, R. M. & Gallop, P. M. Structure of hemoglobin AIc: nature of the N-terminal beta chain blocking group. Biochem Biophys. Res Commun. 32: 86-93, 1968


AIc

Fast HbSickle

Mass Spectrometry

1960 1970 1980 1990 2000 2010 20201950Hemoglobin A1c Elevated in Diabetes

AIc and Diabetes

Normal

Diabetic

Fetal

Rahbar S. An abnormal hemoglobin in red cells of diabetics. Clinica ChimicaActa 22:296-8, 1968

Fast Hb

L.A. Trivelli et al. Hemoglobin components in patients with diabetes mellitus. N Engl J Med 284 (7):353-357, 1971

Fast Hb Higher in People with Diabetes

AIc

Fast HbSickle

1960 1970 1980 1990 2000 2010 20201950Hemoglobin A1c Elevated in Diabetes

AIc and Diabetes

Koenig RJ et al. Correlation of glucose regulation and hemoglobin AIc in diabetes mellitus. NEJM 1976;295:417-20.

AIccorrelated with blood

glucose

AIc

Fast Hb

L.A. Trivelli et al. Hemoglobin components in patients with diabetes mellitus. N Engl J Med 284 (7):353-357, 1971

Fast Hb Higher in People with Diabetes

Sickle

1960 1970 1980 1990 2000 2010 20201950

Sickle

Hemoglobin A1c Elevated in Diabetes

AIc and Diabetes

Koenig RJ et al. Correlation of glucose regulation and hemoglobin AIc in diabetes mellitus. NEJM 1976;295:417-20.

AIccorrelated with blood

glucose

Blo

od G

luco

se (m

g/dl

)B

lood

Glu

cose

(mg/

dl)

00 1010 2020 3030 4040 5050 6060 7070

100100200200300300400400500500600600700700 Type I DiabetesType I Diabetes

Time (days)Time (days)

Assessing GlycemiaAssessing Glycemia

Blood glucose variation within individuals

AIc

Fast Hb

1960 1970 1980 1990 2000 2010 20201950

Sickle

Hemoglobin A1c Elevated in Diabetes

AIc and Diabetes

Blo

od G

luco

se (m

g/dl

)B

lood

Glu

cose

(mg/

dl)

00 1010 2020 3030 4040 5050 6060 7070

100100200200300300400400500500600600700700 Type I DiabetesType I Diabetes

Time (days)Time (days)

Assessing GlycemiaAssessing Glycemia

Blood glucose variation within individuals

R. J. Jarrett; et al. "Instant" blood sugar measurement using Dextrostix and a reflectance meter. Diabetes. 19 (10):724-726, 1970

AIc

Fast Hb

1960 1970 1980 1990 2000 2010 20201950

SickleAIc and

Diabetes

H. F. Bunn; et al. The glycosylation of hemoglobin: relevance to diabetes mellitus. Science 200 (7):21-27, 1978

Two-step model of hemoglobin glycation

Labile A1c Stable A1c

Bunn HF, et al. Further identification of the nature and linkage of the carbohydrate in hemoglobin A1c. Biochem Biophys Res Commun1975;67:103-9

glu

IS

gluman

man?

Gas ChromatographyOf CHO


AIc

Fast Hb

1960 1970 1980 1990 2000 2010 20201950

Sickle

Diabetes Control and Complications Trial

AIc and Diabetes

H. F. Bunn; et al. The glycosylation of hemoglobin: relevance to diabetes mellitus. Science 200 (7):21-27, 1978

Two-step model of hemoglobin glycation

Labile A1c Stable A1c

D. E. Goldstein, et al. In: Methods in Diabetes Research, edited by J. Larner, S. L. Pohl, and W. L Clarke, New York:Wiley, 1986, p. 475-504

A1c

Bio-Rex 70Cation

Exchange

Labile fraction removed by

RBC incubation in physiological saline >5 h

DCCT

Highly Variable

AIc

Fast Hb

1960 1970 1980 1990 2000 2010 20201950

SickleAIc and

Diabetes

D. E. Goldstein, et al. In: Methods in Diabetes Research, edited by J. Larner, S. L. Pohl, and W. L Clarke, New York:Wiley, 1986, p. 475-504

A1c

Bio-Rex 70Cation

Exchange

DCCTFeasibility

The DCCT Research Group. Diabetes Control and Complications Trial (DCCT): results of feasibility study.Diabetes Care 10 (1):1-19, 1987


RBC incubation in physiological saline >5 h

Wide population variation

7-po

int p

rofil

e se

ts


AIc

Fast Hb

1960 1970 1980 1990 2000 2010 20201950

SickleAIc and

DiabetesDCCTFeasibility

The DCCT Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. NEJM 1993;329:977-86.

Effect of Intensive ManagementOn Hemoglobin A1c Levels

Development of RetinopathyPrimary Prevention Cohort

Complications

EDIC


AIc

Fast Hb

Clinical Monitoring of Blood Glucose

1960 1970 1980 1990 2000 2010 20201950

SickleAIc and

DiabetesDCCTFeasibility Complications

Cation Exchange HPLC

Boronate Affinity Chromatography

Immunoaffinity

AIc

Fast Hb

Commercial Glycated Hemoglobin Assays

D. E. Goldstein, et al. Methods for quantitating glycosylated hemoglobins: high performance liquid chromatography and thiobarbituric acid colorimetry. In: Methods in Diabetes Research, edited by J. Larner, S. L. Pohl, and W. L Clarke, New York:Wiley, 1986, p. 475-504

Bio-Rex 70Cation Exchange

HPLC


Immunoaffinity

Non-diabetic

Diabetic

A1c A1c


RBC incubation in

PBS >5 h

1960 1970 1980 1990 2000 2010 20201950

SickleAIc and

DiabetesDCCTFeasibility ComplicationsAIc

Fast Hb




Immunoaffinity

Tosoh A1c 2.2

Khuu et al. Evaluation of a fully automated high-performance liquid chromatography assay for hemoglobin A1c. Arch Pathol Lab Med 123:763-7, 1999

Non-diabeticDiabetic

Good ControlDiabetic

Poor Control

Labile

A1c

1960 1970 1980 1990 2000 2010 20201950

SickleAIc and


Fast Hb




Immunoaffinity

|HO-C

|HO-C

|

Vicinal diol

R. L. Garlick; et al. Characterization of glycosylated hemoglobins. Relevance to monitoring of diabetic control and analysis of other proteins. J Clin Invest 71 (5):1062-1072, 1983

1960 1970 1980 1990 2000 2010 20201950

SickleAIc and


Fast Hb


|HO-C

|HO-C

|

Vicinal diol

R. L. Garlick; et al. Characterization of glycosylated hemoglobins. Relevance to monitoring of diabetic control and analysis of other proteins. J Clin Invest 71 (5):1062-1072, 1983

Add mixture ofglycated and non-glycatedhemoglobins

Non-diol hemoglobins pass through (N, non-glycated)

Hemoglobins modified by vicinal diols bind (G, glycated)


Doesn’t measure

labile A1c

1960 1970 1980 1990 2000 2010 20201950

SickleAIc and


Fast Hb




ImmunoaffinityAntibodies made from

synthetic N-terminal beta globin peptides or purified A1c

chromatography fractions

Doesn’t measure

labile A1c

1960 1970 1980 1990 2000 2010 20201950

SickleAIc and


Fast Hb


Immunoaffinity

A1c

Whatever is present inthe A1c peak;

modified Val1

What do these assays measure?

Whatever is present inthe bound fraction;vicinal diols on any

amino group

Whatever the antibody

recognizes



1960 1970 1980 1990 2000 2010 20201950

SickleAIc and

Diabetes Feasibility ComplicationsAIc

Fast Hb

National Glycohemoglobin Standardization Program



Immunoaffinity

A1c

DCCT NGSP

DCCT Bio-Rex 70 Cation Exchange Reference Method

1960 1970 1980 1990 2000 2010 20201950

SickleAIc and

Diabetes Feasibility ComplicationsAIc

Fast Hb

National Glycohemoglobin Standardization Program

DCCT NGSP

MinutesMinutesA

A

415

415

AA22 FF

SS

AA1c1c

AA00

5 6 7 8 9 10 11 12 13 14 150.00

0.02

0.040.04

0.06

0.08cIEFcIEF –– Sickle Cell TraitSickle Cell Trait

1960 1970 1980 1990 2000 2010 20201950

AIc and DiabetesSickle Complications

DCCTFeasibility

CIEF for hemoglobinopathies

Hempe JM, Craver RD. Quantification of hemoglobin variants by capillary isoelectric focusing. Clin Chem 40:2288-95, 1994

A1c

Capillary ElectrophoresisCapillary Electrophoresis

AnodeAnodeBufferBuffer

CathodeCathodeBufferBuffer

Sample Sample InjectionInjection

CapillaryCapillaryOutletOutlet

Detector50 50 µµm i.d.m i.d.27 cm long27 cm long

AutosamplerAutosampler

CapillaryCapillaryInletInlet

High VoltageHigh VoltagePower SupplyPower Supply

++ --

Children’s Hospital Studies

AIc

Fast Hb NGSP

1960 1970 1980 1990 2000 2010 20201950

AIc and DiabetesSickle Complications

DCCTFeasibility

Hempe JM, Vargas A, Craver RD. In: Petersen JR, Mohammad AA, eds. Clinical and Forensic Applications of Capillary Electrophoresis. Totowa, NJ: Humana Press, 2001:145-63

vs DCCT Assay

cIEFcIEF CorrelationCorrelation

0 5 10 15 200

5

10

15

20

25

5 10 15 20 25% % HbHb AA1c 1c (HPLC (HPLC -- Overnight incubation)Overnight incubation)

%

% H

bH

bAA

1c

1c (( c

IEF

cIEF

))

cIEFcIEF18 h incubation18 h incubation

cIEFcIEF6 h incubation6 h incubation

y =1.33x y =1.33x -- 1.401.40rr22=0.95, n=21=0.95, n=21

y =1.07x + 1.28y =1.07x + 1.28rr22=0.94, n=40=0.94, n=40

cIEFcIEF Reference RangeReference Range

Num

ber o

f Obs

erva

tions

Num

ber o

f Obs

erva

tions

% % HbHb AA1c1c

4 6 8 10 12 14 16 18 20 22 240

15

30

45

Correlation studyCorrelation studynn 139139MeanMean 12.7%12.7%

Normal subjects Normal subjects AgeAge >1 y>1 ynn 124124MeanMean 6.8%6.8%SDSD 0.80.8Range Range 5.3 5.3 -- 8.4%8.4%

CIEF for hemoglobinopathiesA1c

Children’s Hospital Studies

AIc

Fast Hb NGSP

1960 1970 1980 1990 2000 2010 20201950

SickleAIc and



Comparison of A1c and MBG in

Children

A1c and

A1c

Hemoglobin Glycation Index

AIc

Fast Hb NGSP

1960 1970 1980 1990 2000 2010 20201950

SickleAIc and



Comparison of A1c and MBG in

Children

A1c and

A1c


AIc

Fast HbFeasibility

The DCCT Research Group. Diabetes Control and Complications Trial (DCCT): results of feasibility study.Diabetes Care 10 (1):1-19, 1987

Wide population variation

7-po

int p

rofil

e se

ts

NGSP

Mean Blood Glucose (mg/dl)Mean Blood Glucose (mg/dl)

% H

bA1c

% H

bA1c

00 100100 200200 300300 400400

AA

551010151520202525

High HGPHigh HGP

Low HGPLow HGP

ModerateModerateHGPHGP

ChildrenChildren’’s Hospital s Hospital Study:Study:

2.3 years2.3 years128 children128 children

Type 1 diabetesType 1 diabetes

HbA1c levels are HbA1c levels are influenced by factors in influenced by factors in

addition to glucoseaddition to glucose

Hemoglobin Glycation Hemoglobin Glycation PhenotypesPhenotypes

Hempe et al. J Diab Comp 16:313,2002

BB

551010151520202525

Three individual patients

Hemoglobin Glycation IndexHemoglobin Glycation IndexHGI = Observed HGI = Observed -- Predicted HbA1cPredicted HbA1c

Predicted HbA1c = (MBG Predicted HbA1c = (MBG ×× slope) + interceptslope) + intercept


% H

bA1c

% H

bA1c

00 100100 200200 300300 400400 500500 600600

5510101515202025253030

HGI=0HGI=0

HGI<0HGI<0

HGI>0HGI>0


% H

bA1c

% H

bA1c

00 100100 200200 300300 400400

AA

55

1010

1515

55

1010

1515BB High HGPHigh HGP

Low HGPLow HGP

n=1441n=1441

Diabetes Control and Complications Trial (DCCT)Diabetes Control and Complications Trial (DCCT)

--2.22.2 --1.21.2 --0.20.2 0.80.8 1.81.8 2.82.800

5050

100100

150150Low HGPLow HGP

Moderate HGPModerate HGP

High HGPHigh HGP

HGIHGIFr

eque

ncy

Freq

uenc

y

Hypothesis: High HGP patientsHypothesis: High HGP patientsare more susceptible toare more susceptible tomicrovascular complicationsmicrovascular complications

Three individual patients

First 100 patients

ModerateModerateHGPHGP

Diabetes Control and Complications Trial (DCCT)Diabetes Control and Complications Trial (DCCT)

0.020.02

0.040.04

0.060.06

0.080.08

0.100.10NephropathyNephropathy

Ris

k Pr

obab

ility

Ris

k Pr

obab

ility

00 11 22 33 44 55 66 77

Years of FollowYears of Follow--upup

0.050.050.100.100.150.150.200.200.250.250.300.300.350.35

RetinopathyRetinopathy

--2.22.2 --1.21.2 --0.20.2 0.80.8 1.81.8 2.82.800

5050

100100

150150Low HGPLow HGP

Moderate HGPModerate HGP

High HGPHigh HGP

HGIHGIFr

eque

ncy

Freq

uenc

yConclusion: HGI reflects Conclusion: HGI reflects biological variation in A1c and biological variation in A1c and complications risk due to factors complications risk due to factors other than mean blood glucoseother than mean blood glucoseMcCarter et al. Diabetes Care 27: 1259, McCarter et al. Diabetes Care 27: 1259, 20042004

HGI and Biological Variation in A1cStudy Reference Patients A1c Blood glucose

Children’s Hospital

JDC 2002 Type 1 children

CIEF MBG - 30 d meter data

DCCT Diabetes Care 2004

Type 1 adults

BioRex HPLC

MBG - 7 pt profile set

UKPDS ADA 2005

Type 2 adults

BioRad HPLC

Fasting glucose

DirecNet Diabetes Care 2007

Type 1 children

NGSPImmunoassay

MBG - CGM

Children’s Hospital

Pediatric Diab 2010

Type 1 children

NGSPImmunoassay

MBG – Raw meter data

100

150

200

250

300

100

150

200

250

300 MBG

6789

101112 A1C

6789101112

%

m

g/dl

Sequential Clinic Visits

ModerateLow High

-4

-2

0

2

4 HGI

-4

-2

0

2

4

%

Soros AA, Chalew SA, McCarter RJ, Shepard R, Hempe JM. Hemoglobin glycation index: a robust measure of hemoglobin A1c bias in pediatric type 1 diabetes patients. Pediatric Diabetes 11:455-461, 2010

1960 1970 1980 1990 2000 2010 20201950

SickleAIc and



HGI


AIc

Fast Hb

A1c

IFCCNGSP

Diabetes Care 30(9):2399-2400, 2007

1. The NGSP cation exchange reference A1c method is non-specific2. The IFCC developed a mass spectrometry based reference method

that quantifies N-terminal hexapeptides of globin modified by glucose

3. IFCC standardized results were 25% lower than NGSP standardized results

4. Recommended reporting A1c in mmol A1c/mol of Hb5. And since MBG = A1c, consider reporting A1c as “estimated

average glucose” - eAG

AG

(mg/

dl)

Nathan DM, Kuenen J, Borg R, Zheng H, Schoenfeld D, Heine RJ. Translating the A1C Assay Into Estimated Average Glucose Values. Diabetes Care 31:1-6, 2008

HbA1c (%) Average of 4 different assays

CG

M +

SM

BG

AG (mg/dl) = 28.7 x HbA1c – 46.7r2 = 0.84, p < 0.0001

Underlying assumption: A1c is related to MBG the same way in all people

Diabetes Care 31:1-6, 2008

Diabetologia 51:904, 2008

Brick, J. C. et al. (2009) A Randomized Comparison of the Terms Estimated Average Glucose Versus Hemoglobin A1C. Diabetes Educ. 35: 596-602.

eAG does not improve patient understanding

of diabetes management

Low Moderate High75

100

125

150

175

200

225

250 MBGeAG

HGI Group

mg/

dl

eAG<MBGunderestimates

eAG = 28.7 A1c - 46.7

eAG=MBG

eAG>MBGoverestimates

Hempe, J.M., Soros, A.A. & Chalew, S.A. Diabetes Care 33:1449, 2010

A1c 6% = eAG of 126

Low Moderate High75

100

125

150

175

200

225

HGI Group

4

5

6

7

8

9

10MBGA1c

MB

G (m

g/dl

)

A1c (%

)

Failure to reachtarget MBG Exceed target

MBG/risk forhypoglycemia

American Diabetes Association. Standards of medical care in diabetes--2010. Diabetes Care 2010;33 Suppl 1:S11-S61.

Low Moderate High75

100

125

150

175

200

225

HGI Group

4

5

6

7

8

9

10MBGA1c

MB

G (m

g/dl

)

A1c (%

)



Low Moderate High75

100

125

150

175

200

225

HGI Group

4

5

6

7

8

9

10MBGA1c

MB

G (m

g/dl

)

A1c (%

)



American Diabetes Association. Standards of medical care in diabetes--2010. Diabetes Care 2010;33 Suppl 1:S11-S61.

Diabetes Care 32 (7):1327-1334, 2009

Non-proliferative retinopathy graded by fundus photography(n=28,000 from 9 countries)

van 't Riet E.; et al. Relationship between A1C and glucose levels in the general Dutch population: the new Hoorn study. Diabetes Care 33 (1):61-66, 2010.

NG

DiabetesBoth

DiabetesOGTT

DiabetesA1c

NG

DiabetesBoth

DiabetesFPG

DiabetesA1c

Hypoglycemia

Hyperglycemia

Coma and Death

Microvascular and Macrovascular Disease

Acute Chronic

InsulinMetformin + sulfonylureas

Hypoglycemia

Currie CJ, et al. Survival as a function of HbA1c in people with type 2 diabetes: a retrospective cohort study. The Lancet 2010;In Press, Corrected Proof.

Diabetes Care 33:1025-1027, 2010

Clinical Research Basic Research

Hemoglobin Analysis

Analysis of Existing

Clinical Trial Data

Prospective Diabetes

Study

Mechanisms of Non-enzymatic

Hemoglobin Glycation

Mouse Model of

Hemoglobin Glycation

Best way to use HGI and

hemoglobin assays to

improve patient care

HGI association with clinical phenotype

and outcome in large populations

Quantitative in vitro bioassay of non-

enzymatic hemoglobin

glycation

In vivo assessment of factors that influence non-

enzymatic hemoglobin

glycation

Development of multidimensional hemoglobin separation techniquesIdentification of chemical modifiers

Translational Research Program

1.1. Describe what clinical laboratories actually Describe what clinical laboratories actually measure as HbA1cmeasure as HbA1c

2.2. Show that HbA1c and mean blood glucose are Show that HbA1c and mean blood glucose are not interchangeable estimates of glycemic not interchangeable estimates of glycemic controlcontrol

3.3. Explain how biological variation in HbA1c Explain how biological variation in HbA1c complicates new guidelines for the diagnosis complicates new guidelines for the diagnosis and management of diabetesand management of diabetes

ObjectivesObjectives

1.1. MBG MBG A1cA1c2.2. Consider both MBG and A1c for more Consider both MBG and A1c for more

personalized patient carepersonalized patient care3.3. Even expert committee recommendations Even expert committee recommendations

should be taken with a grain of saltshould be taken with a grain of salt

ConclusionsConclusions

SS Medical-Industrial Complex

It Takes a Long Time to Change Course

FundingFundingChildrenChildren’’s Hospital RICs Hospital RICADA, JDRF, ADA, JDRF, P & C Carroll FoundationP & C Carroll Foundation

StudentsStudentsAmanda McGeeheeAmanda McGeeheeRachel ShepardRachel ShepardAllyson BazarskyAllyson BazarskyThanksThanksChildrenChildren’’s Hospital Labs Hospital LabEndocrine NursesEndocrine Nurses

CollaboratorsCollaboratorsStuart Chalew, M.D.Stuart Chalew, M.D.Bob McCarter, Sc.D.Bob McCarter, Sc.D.Alfonso Vargas, M.D.Alfonso Vargas, M.D.Ricardo Gomez, M.D.Ricardo Gomez, M.D.Randal Craver, M.D.Randal Craver, M.D.Arlette Soros, M.D.Arlette Soros, M.D.

"An important scientific innovation rarely makes its way by gradually winning over and converting its opponents. What does happen is that its opponents gradually die out and that the growing generation is familiar with the idea from the beginning."

Max Planck1858-1947

hemoglobin a1c in the diagnosis and management of diabetes grand... · hemoglobin a1c in the...

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