changes in levels of haemoglobin a 1c during the first 6 years after diagnosis of clinical type 2...
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Changes in levels of haemoglobin A1c during the first 6 years after
diagnosis of clinical type 2 diabetes
Clinical implications
Niels de Fine OlivariusVolkert SiersmaLars J. Hansen
Thomas DrivsholmMogens Hørder
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Glucose-lowering trials in type 2 diabetes
UGDP1970
: 2.9 times higher death rate from CVD in tolbutamide group (p=0.005 vs. placebo)
UKPDS1998
: 96% increase in DM-related death for those treated with both metformin and sulfonylurea (p=0.04 vs. conventional / sulphonylurea)
Metaanalysis 2007
: Rosiglitazone: 64% increase in deaths from CVD (p=0.06 vs. placebo or other agents)
ACCORD2008
: 35% increase in deaths from CVD (p=0.02 vs. less intensive glucose-lowering therapy)
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Lesson to be learned
Treatment regimens aiming at normalizing blood glucose for all patients may be detrimental,
at least in middle-aged and older adults with diabetes of long duration.
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Against generalized thought
Average figures used to describe changes in HbA1c may conceal a clinically important diversity in the way the blood glucose level deteriorates or even improves, especially immediately after diabetes diagnosis.
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Objective
To assess the variability in levels of glycosylated haemoglobin (HbA1c) during the first six years after diagnosis of clinical type 2 diabetes in relation to possible predictors.
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Flow chart
Newly diagnosed diabetic patients from the intervention
group, n=718
Patients who did not have at least three measurements of HbA1c, n=97
Missing HbA1c-measurement within 90 days after diabetes diagnosis, n= 40
Patients for analysis of predictors of course of HbA1c, n=621
Patients for figures showing the course of HbA1c, n=581
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All measurements of HbA1c
Upper limit of reference range
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HbA1c for 50 randomly selected patients
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Modelling the course of HbA1c
Years since diabetes diagnosis
Hae
mog
lobi
n A1
c (%
)
Level of HbA1c
one year afterdiabetes diagnosis
Slope of theHbA1c-curve
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Predictors of level and slope of HbA1c
Gender
Age
BMI
HbA1c
Systolic BP
Total cholesterols
Urinary albumin
Multivariate linear regression models
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Predictors of level and slope of HbA1c
Gender
Age
BMI
HbA1c
Systolic BP
Total cholesterols
Urinary albumin
Diabetic retinopathy
Coronary heart disease
Peripheral vascular disease
Peripheral neuropathy
Familial disposition to diabetes
Smoking
Physical activity
Marital status
Residence
GP's acquaintance with the patient
Multivariate linear regression models
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Predictors of level and slope of HbA1c
Gender
Age
BMI
HbA1c
Systolic BP
Total cholesterols
Urinary albumin
Diabetic retinopathy
Coronary heart disease
Peripheral vascular disease
Peripheral neuropathy
Familial disposition to diabetes
Smoking
Physical activity
Marital status
Residence
GP's acquaintance with the patient
Multivariate linear regression models
SLOPE
LEVEL
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Changes in HbA1c according to HbA1c at diagnosis
Years since diabetes diagnosis
HbA1c > 10%
Hae
mog
lobi
n A 1c
(%)
HbA1c ≤ 10%
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Changes in HbA1c according to age
Years since diabetes diagnosis
Hae
mog
lobi
n A 1c
(%)
Age ≤ 65 y.
Age > 65 y.
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Years since diabetes diagnosis
HbA1c > 10 at diagnosis
Hae
mog
lobi
n A 1c
(%)
Patients are grouped according to quartiles of the slope of HbA1c after 1-year follow-up
Changes in HbA1c (I)From generalisation to individualisation
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Changes in HbA1c (II)From generalisation to individualisation
Years since diabetes diagnosis
HbA1c ≤ 10 at diagnosis
Hae
mog
lobi
n A 1c
(%)
Patients are grouped according to quartiles of the slope of HbA1c after 1-year follow-up
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Conclusion 1
ACCORD – ADVANCE – VADT – UKPDS – UGDP
Lowering glucose levels for all patients with T2DM
has limited benefit and can lead to significant harm
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Conclusion 2
Diabetes Care in General PracticeIndividualization:
A more appropriate strategy to reduce the level and variability of HbA1c could be to
monitor changes in HbA1c more closely and intensify treatment of those patients who
actually experience the beginning of an apparently inexorable deterioration of their
glycaemic control
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Years since diabetes diagnosis
HbA1c > 10 at diagnosis
Hae
mog
lobi
n A 1c
(%)
Patients are grouped according to quartiles of the slope of HbA1c after 1-year follow-up
Changes in HbA1c (I)From generalisation to individualisation
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DCGP vs. UKPDS
Years since diabetes diagnosis
Fasti
ng p
lasm
a gl
ucos
e (m
mol
/l)
conventional treatment
intensive treatment
structured care
comparisongroup (=conventionaltreatment)
UKPDSDCGP
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DCGP vs. UKPDS
% treated with diet alone
Fasti
ng p
lasm
a gl
ucos
e (m
mol
/l)
UKPDSDCGP
90%70%
45%
17%7%
13%
55%40%
29% 32%
Years since diabetes diagnosis
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HbA1ccross-sectional, median values
06
7
8
9
0 3 6 9 12 15
HbA
1c
(%)
Years from randomisation
Conventional
Intensive
UKPDS