hb a1c goals
TRANSCRIPT
In diabetics, does a HbA1c
goal of 7.0 vs. 6.5 result in
less microvascular disease
and all cause mortality?Daniel Wu
ADA Standards of Medical Care 2012 Goals should be individualized based on
○ duration of diabetes
○ age/life expectancy
○ comorbid conditions
○ known CVD or advanced microvascular complications
○ hypoglycemia unawareness
○ individual patient considerations
More- or less-stringent glycemic goals may be appropriate for
individual patients
Postprandial glucose may be targeted if A1C goals are not
met despite reaching preprandial glucose goals
Lowering A1C to below or around 7% has been shown to reduce
microvascular complications of diabetes, and if implemented soon
after the diagnosis of diabetes is associated with long-term
reduction in macrovascular disease. Therefore, a reasonable A1C
goal for many nonpregnant adults is <7%. (B)
Providers might reasonably suggest more stringent A1C goals (such
as <6.5%) for selected individual patients, if this can be achieved
without significant hypoglycemia or other adverse effects of
treatment. Appropriate patients might include those with short
duration of diabetes, long life expectancy, and no significant
CVD. (C)
ADA Standards of Medical Care 2012
AACE Guidelines for Diabetes Plan 2011
Glucose targets should be individualized and take into account
residual life expectancy,
duration of disease,
presence or absence of microvascular and macrovascular
complications,
CVD risk factors,
comorbid conditions
risk for severe hypoglycemia.
Glucose targets should also be formulated in the context of the
patient’s psychological, social, and economic status
AACE Guidelines for Diabetes Plan 2011
In general, therapy should target a A1C level of 6.5% or
less for most nonpregnant adults, if it can be achieved
safely.
In certain patients, a less stringent goal may
be considered (A1C 7%-8%).
Such individuals as those with history of severe
hypoglycemia, limited life expectancy, advanced
microvascular or macrovascular complications,
extensive comorbid conditions, or long-standing DM in
which the general goal has been difficult to attain despite
intensive efforts
Same Evidence Base
Diabetes Control and Complications Trial
(1993)
U.K. Prospective Diabetes Study
(2000)
Diabetes Control and Complications Trial
Will intensive therapy prevent the development of diabetic
retinopathy in patients with no retinopathy (primary
prevention)
Will intensive therapy affect the progression of early
retinopathy (secondary intervention)?
Retinopathy was the principal study outcome, but they also
studied renal, neurologic, cardiovascular, and
neuropsychological outcomes and the adverse effects of the
two treatment regimens.
Eligibility Criteria
The major criteria for eligibility included
insulin dependence, as evidenced by deficient C-peptide
secretion;
an age of 13 to 39 years
absence of hypertension
absence of hypercholesterolemia
absence of severe diabetic complications or medical conditions
Therapy
Conventional therapy consisted of one or two daily injections of insulin, including mixed intermediate and rapid-acting insulins, daily self-monitoring of urine or blood glucose, and education about diet and exercise
Intensive therapy included the administration of insulin three or more times daily by injection or an external pump. The dosage was adjusted according to the results of self-monitoring of blood glucose performed at least four times per day, dietary intake, and anticipated exercise.
The goals of intensive therapy included preprandial blood glucose concentrations between 70 and 120 mg per deciliter (3.9 and 6.7 mmol per liter), postprandial concentrations of less than 180 mg per deciliter (10 mmol per liter), a weekly 3-a.m. measurement greater than 65 mg per deciliter (3.6 mmol per liter), and hemoglobin A1c (glycosylated hemoglobin), measured monthly, within the normal range (less than 6.05 percent).
A1c Levels
Differences in Intervention Outcomes:
Retinopathy in Cohorts
Differences in Intervention Outcomes
Rate of Progression of Retinopathy vs.
Rate of Severe Hypoglycemia
U.K. Prospective Diabetes Trial
To determine the relation between exposure to glycemia over
time and the risk of macrovascular or microvascular
complications in patients with type 2 diabetes.
Primary predefined aggregate clinical outcomes: any end
point or deaths related to diabetes and all cause mortality.
Secondary aggregate outcomes: myocardial infarction,
stroke, amputation (including death from peripheral vascular
disease), and microvascular disease (predominantly retinal
photo-coagulation).
Participants
The 3867 patients who had fasting plasma glucose
concentrations between 6.1 and 15.0 mmol/l and no
symptoms of hyperglycemia were randomized to a policy of
conventional glucose control, primarily with diet, or to an
intensive policy with sulfonylurea or insulin.
Stratton I M et al. BMJ 2000;321:405-412
©2000 by British Medical Journal Publishing Group
Incidence Rates for MI and Microvascular Complications
Stratton I M et al. BMJ 2000;321:405-412
©2000 by British Medical Journal Publishing Group
Hazard Ratios for Any End Point, Death, and All Cause Mortality
ACCORD Trial: Glycemic Control
Investigated whether intensive therapy to target normal
glycated hemoglobin levels would reduce cardiovascular
events in patients with type 2 diabetes who had either
established cardiovascular disease or additional
cardiovascular risk factors.
10,251 patients (mean age, 62.2 years) with a median
glycated hemoglobin level of 8.1% were assigned to receive
intensive therapy (targeting a glycated hemoglobin level
below 6.0%) or standard therapy (targeting a level from 7.0
to 7.9%).
HbA1c Levels Achieved
Primary Outcomes
This trend was not
significant, with rates
of 6.9% in the
intensive-therapy
group and 7.2% in
the standard-therapy
group (hazard ratio,
0.90; 95%
confidence interval
[CI], 0.78 to 1.04;
P=0.16)
All Cause Mortality
The rate of death
from any cause
was higher in the
intensive-therapy
group than in the
standard-therapy
group (5.0% vs.
4.0%; hazard ratio,
1.22; 95% CI, 1.01
to 1.46; P=0.04).
Cessation of Study
The finding of higher mortality in the intensive-therapy group
led to a decision to terminate the intensive regimen in
February 2008, 17 months before the scheduled end of the
study.
Rates of death in the two study groups began to separate
after 1 year, and the differences persisted throughout the
follow-up period.
The effect on mortality was consistent within the subgroups
with no evidence of heterogeneity and persisted in models
adjusting for differences in the receipt of medications for
blood pressure and lipids.
Adverse Events
Analysis of the ACCORD Trial
The prespecified composite outcomes were
dialysis or renal transplantation
high serum creatinine (>291.7 μmol/L) or retinal photocoagulation
or vitrectomy (first composite outcome)
or peripheral neuropathy plus the first composite outcome
(second composite outcome)
Faramarz Ismail-Beigi , Timothy Craven , Mary Ann Banerji , Jan Basile , Jorge Calles , Robert M Cohen , Robert C...
Effect of intensive treatment of hyperglycaemia on microvascular outcomes in type 2 diabetes: an analysis of the ACCORD
randomised trial
The Lancet Volume 376, Issue 9739 2010 419 - 430
http://dx.doi.org/10.1016/S0140-6736(10)60576-4
Primary Composite Outcomes
All Microvascular Outcomes
Analysis of the ACCORD Trial
The primary composite outcome of advanced nephropathy
and diabetic eye complications did not differ between groups
at transition or at study end.
The second composite endpoint, which added a peripheral
neuropathy outcome to the primary composite outcome, also
did not differ at transition or at study end.
Intensive glycemia therapy led to a 21% reduction in
development of microalbuminuria at transition and this effect
was attenuated (15%) but remained significant at study end.
Incidence of macroalbuminuria was reduced in the intensive
group compared with the standard group at transition and at
study end.
Changes to ADA Recommendations
Providers might reasonably suggest more stringent A1C
goals (such as <6.5%) for selected individual patients, if this
can be achieved without significant hypoglycemia or other
adverse effects of treatment. Appropriate patients might
include those with short duration of diabetes, long life
expectancy, and no significant cardiovascular disease. (C)
Less stringent A1C goals (such as <8%) may be appropriate
for patients with a history of severe hypoglycemia, limited life
expectancy, advanced microvascular or macrovascular
complications, extensive comorbid conditions, and those with
longstanding diabetes in whom the general goal is difficult to
attain despite diabetes self-management education,
appropriate glucose monitoring, and effective doses of
multiple glucose-lowering agents including insulin. (B)
Conclusions from Studies
DCCT
Intensive therapy of patients delays the onset and slows the
progression of clinically important retinopathy, including vision-
threatening lesions, nephropathy, and neuropathy, by a range of
35 to more than 70 percent.
Because of the risk of hypoglycemia, intensive therapy should be
implemented with caution, especially in patients with repeated
severe hypoglycemia or unawareness of hypoglycemia.
UKPDS
No threshold of glycemia was observed for a substantive change
in risk for any of the clinical outcomes examined
The lower the glycemia the lower the risk of complications
Suggests that there is no specific target value of hemoglobin
A1c for which one should aim but that the nearer to normal the
hemoglobin A1c concentration the better.
Conclusions from Studies
ACCORD
No significant effect of intensive glycemia therapy on the two
prespecified composite microvascular outcomes—1) advanced
renal or eye complications, or 2) these two outcomes or
peripheral neuropathy.
The beneficial effects of intensive therapy on surrogate
secondary microvascular outcomes compared with standard
therapy should be balanced against observed risks.
Therapeutic strategy targeting HbA1c levels of 6.0% increased
the rate of all cause death as compared with a target level of 7.0
to 7.9%.
Recommendation for Patient
Target level for HbA1c of 7.0%
Long duration of diabetes and significant CVD- rules out the
criteria for possible intensive management
Side effects of intensive therapy: weight gain, fluid retention,
and hypoglycemia
Benefit of decreased micro- and macroalbuminuria does not
outweigh the side effects of intensive therapy
Target of 7.0% has a significantly lower risk of all cause death
General goal of attaining the 7.0% is difficult for many patients
and is reasonable to reduce microvascular disease and all cause
death
References1. Laakso M, Cederberg H. Glucose control in diabetes: which target level to aim for? J Intern Med. 2012
Jul;272(1):1-12. doi: 10.1111/j.1365-2796.2012.02528.x. Epub 2012 Mar 13. Review. PubMed PMID: 22321169.
2. Introduction: The American Diabetes Association's (ADA) evidence-based practice guidelines, standards, and related recommendations and documents for diabetes care. Diabetes Care. 2012 Jan;35 Suppl 1:S1-2. PubMed PMID: 22187466.
3. Handelsman Y, Mechanick JI, Blonde L, Grunberger G, Bloomgarden ZT, Bray GA, Dagogo-Jack S, Davidson JA, Einhorn D, Ganda O, Garber AJ, Hirsch IB, Horton ES, Ismail-Beigi F, Jellinger PS, Jones KL, Jovanovič L, Lebovitz H, Levy P, Moghissi ES, Orzeck EA, Vinik AI, Wyne KL; AACE Task Force for Developing Diabetes Comprehensive Care Plan. American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for developing a diabetes mellitus comprehensive care plan. Endocr Pract. 2011 Mar-Apr;17 Suppl 2:1-53. PubMed PMID: 21474420.
4. Ismail-Beigi F, Craven T, Banerji MA, Basile J, Calles J, Cohen RM, Cuddihy R, Cushman WC, Genuth S, Grimm RH Jr, Hamilton BP, Hoogwerf B, Karl D, Katz L, Krikorian A, O'Connor P, Pop-Busui R, SchubartU, Simmons D, Taylor H, Thomas A, Weiss D, Hramiak I; ACCORD trial group. Effect of intensive treatment of hyperglycaemia on microvascular outcomes in type 2 diabetes: an analysis of the ACCORD randomised trial. Lancet. 2010 Aug 7;376(9739):419-30. Epub 2010 Jun 30. Erratum in: Lancet. 2010 Oct 30;376(9751):1466. PubMed PMID: 20594588.
5. Action to Control Cardiovascular Risk in Diabetes Study Group, Gerstein HC, Miller ME, Byington RP, Goff DC Jr, Bigger JT, Buse JB, Cushman WC, Genuth S, Ismail-Beigi F, Grimm RH Jr, Probstfield JL, Simons-Morton DG, Friedewald WT. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008 Jun 12;358(24):2545-59. Epub 2008 Jun 6. PubMed PMID: 18539917.
6. Stratton IM, Adler AI, Neil HA, Matthews DR, Manley SE, Cull CA, Hadden D, Turner RC, Holman RR. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ. 2000 Aug 12;321(7258):405-12. PubMed PMID: 10938048; PubMed Central PMCID: PMC27454.