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Cardio Diabetes Medicine 2017 569

seemsunlikely that hyperglycemia does not increase
Cardiovascular risk. The recent studies included
participants with low potential for reversing estab-
lished Cardiovascular disease and high risk of treat-
ment-associated side-effects. Fig. 3 shows a grid with
four subgroups arranged by duration of Diabetes and
evidence for Cardiovascular disease [1].

Off-target effects of treatment:
Cardiovascularmortality in the ACCORD.
A multivariable analysis of baselinepredictors of the
excess mortality with intensive versusstandard gly-
cemic strategies showed only three independent-
predictors. They were baseline A higher than 8.5%,
1c
symptomatic Neuropathy reported bythe participants
and a history of daily Aspirin therapy [1]. High A at
1c
Baseline suggests, alone or in combination, greater Is Glucose Control Important for Prevention
prior hyperglycemic exposure, greater severity of un- of Cardiovascular Disease in Diabetes?
derlying pathophysiologic defects and/or behavioral There is convincing evidence from epidemiological
factors interfering with management. In the whole and pathophysiological studies that hyperglycemia
ACCORD population, each 1% higher average A was has a detrimental effect on Cardiovascular risk profile
1c
associated with 22% higher risk of death. One is that in its own right. It is well known that among patients
the risk of severe hypoglycemia was greater at higher with Type 2 Diabetes, those with higher levels of
rather than lower average [1]. blood glucose and HbA are at greater risk for CVD
1c
The ACCORD trial also recently showed a signifi- [5]. Glycemic fluctuations and chronic hyperglycemia
cant reduction in the rate of nonfatal Cardiovascular are triggers for inflammatory responses via increased
events in a follow-up of its Study population, but that endoplasmic reticulum stress and mitochondrial su-
benefit was offset by an increase in mortality in the peroxide production.Several risk factors for CVD,
original trial [4]. In contrast, no reduction in the rate including Insulin resistance/ hyperinsulinemia, hy-
of Cardiovascular events or in mortality was found in perglycemia, overweight/ obesity, haemorheological
a follow up of the ADVANCE trial [4]. abnormalities, dyslipidemia and hypertension, are of-
ten present in varying combinations in patients with
The extended follow-up study of the VADT showed Type 2 Diabetes [5].
that a current multidrug glycemic treatment regimen
can be associated with a significant reduction in ma- It should also be considered that the impact of hy-
jor Cardiovascular events among older patients who perglycemia on Cardiovascular risk could be different
have had Diabetes for many years [4]. in Type 1 and Type 2 Diabetes. Patients with Type 2
Diabetes are heterogeneous for age, duration of dis-
One size does not fit all ease, comorbidity and genetic background. Glucose
lowering therapy should be adapted to this complexi-
With the strong and consistent epidemiologic data ty, with an attempt at improving, or at least avoidance
andthe long-term results of the DCCT and UKPDS, it
of worsening, associated Cardiovascular risk factors.

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