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568 Tight Glycemic Control Decreases Cardio Vascular Mortality
(Proponent)

strating a link between autonomic imbalance, inflam- Endpoints.Total and Cardiovascular mortality were
mation and CVD [3]. unchanged withthe intensive regimens in ADVANCE.

Another Meta-Analysis, also using weighted data
Can glycemic intervention reduce from each study rather than patient level data, added
cardiovascular risks? the main UKPDS and the UKPDS obese sub-study to
Five large studies seeking lower glycemic targets the results of ADVANCE, VADT and ACCORD [1]. It
have been completed . showed a significant 10% reduction in a Cardiovas-
cular composite endpoint driven mainly by 16% lower
risk of nonfatal MI and also no significant changes in
all cause or Cardiovascular mortality. Heterogeneity
between the studies was apparent for all cause and
Cardiovascularmortality, with ACCORD being the out-
lier withunfavorable outcomes [1].

Temporal relationships: the Legacy effect in
the DCCT and UKPDS

In the DCCT/EDIC follow-up, a broad composite Car-
diovascular endpoint was reduced 42% (P¼0.02) and
the composite of Cardiovascular death, nonfatal MI
or nonfatal Stroke was reduced 57% (P¼0.02). In the
UKPDS follow-up, relative risk reductions after inten-
sive treatment with Insulin or a Sulfonylurea were 13%
(P¼0.007) for all-cause mortality and 15% (P¼0.01) for
The earlier randomized Studies the DCCT in Type 1 fatal or nonfatal MI. These findings support intensive
Diabetes and the UKPDS in Type 2 Diabetes both management of hyperglycemia early in Diabetes and
showed that intensive glycemic control can reduce predict that studies may require up to 10 or more
Microvascular complications more than a conven- years of follow-up to demonstrate benefits [1]. Alter-
tional regimen. However, both failed to verify Car- natively, the beneficial effect of intensive therapy on
diovascular benefits. Specifically, the DCCT showed the risk of Cardiovascular disease may be a result of
a non-statistically significant 41% reduction of a broad the reduction in the incidence of micro-vascular dis-
Cardiovascular composite endpoint accompanying ease. Both Renal disease and Autonomic Neuropathy
6.5 years of randomized treatment achieving a 2% have been proposed as risk factors for Cardiovascu-
between-group A differential [1]. lar disease. To the extent that intensive therapy re-
1c
duces these risk factors, Cardiovascular disease may
The main UKPDS found 16% fewer (P¼0.052) fatal or also be reduced[2].
nonfatal MI events and 21% less nonfatal MI (P¼0.057),
accompanying 0.9% lower A during a 10-year period. The legacy concept is relevant to the ADVANCE,
1c
Potential explanations for these inconclusive results VADT and ACCORD Studies, in which participants
include low Cardiovascular event rates in the rela- with well-established Cardiovascular Disease were
tively healthy populations studied and the failure of intentionally selected for Study. For such persons
intensive treatment to obtain nearly normal glucose with long-term hyperglycemia and established tissue
levels. In both studies, the participants were relative- injury, glucose lowering may have little effect on es-
ly young and had recently diagnosed Diabetes and tablished Cardiovascular risk due to a legacy effect in
in neither study were participants required to have reverse. That is, just as the structural and functional
Cardiovascular risk factors other than Diabetes. Both changes of advanced Diabetic Retinopathy and Ne-
studies achieved A levels averaging close to 7.0% phropathy are not reversed by late glycemic interven-
1c
with intensive treatment, although glycemic control tion, structurally advanced Cardiovascular Disease
deteriorated over time in the UKPDS [1]. may not respond well to Glycemic Control [1].
In the more recent studies high-risk patients wereen-
rolled and thus event rates were high. These studies-
confirmed that Microvascular events can be reduced
insuch patients, but also failed to show benefit of
intensivetreatment on their primary Cardiovascular

GCDC 2017