"Intensive blood glucose control and vascular outcomes in patients
with type 2 diabetes," by the ADVANCE Collaborative Group (A.
Patel, et al.), New England Journal of Medicine, 358(24):
2560-72, 12 June 2008.
Abstract:Background: "In patients with
type 2 diabetes, the effects of intensive glucose control on vascular
outcomes remain uncertain.
Methods: We randomly assigned 11,140 patients with type 2
diabetes to undergo either standard glucose control or intensive glucose
control, defined as the use of gliclazide (modified release) plus other
drugs as required to achieve a glycated hemoglobin value of 6.5% or less.
Primary end points were composites of major macrovascular events (death
from cardiovascular causes, nonfatal myocardial infarction, or nonfatal
stroke) and major microvascular events (new or worsening nephropathy or
retinopathy), assessed both jointly and separately.
Results: After a median of 5 years of follow-up, the mean
glycated hemoglobin level was lower in the intensive-control group (6.5%)
than in the standard-control group (7.3%). Intensive control reduced the
incidence of combined major macrovascular and microvascular events (18.1%,
vs. 20.0% with standard control; hazard ratio, 0.90; 95% confidence
interval [CI], 0.82 to 0.98; P=0.01), as well as that of major
microvascular events (9.4% vs. 10.9%; hazard ratio, 0.86; 95% CI, 0.77 to
0.97; P=0.01), primarily because of a reduction in the incidence of
nephropathy (4.1% vs. 5.2%; hazard ratio, 0.79; 95% CI, 0.66 to 0.93;
P=0.006), with no significant effect on retinopathy (P=0.50). There were no
significant effects of the type of glucose control on major macrovascular
events (hazard ratio with intensive control, 0.94; 95% CI, 0.84 to 1.06;
P=0.32), death from cardiovascular causes (hazard ratio with intensive
control, 0.88; 95% CI, 0.74 to 1.04; P=0.12), or death from any cause
(hazard ratio with intensive control, 0.93; 95% CI, 0.83 to 1.06; P=0.28).
Severe hypoglycemia, although uncommon, was more common in the
intensive-control group (2.7%, vs. 1.5% in the standard-control group;
hazard ratio, 1.86; 95% CI, 1.42 to 2.40; P<0.001).
Conclusions: A strategy of intensive glucose control,
involving gliclazide (modified release) and other drugs as required, that
lowered the glycated hemoglobin value to 6.5% yielded a 10% relative
reduction in the combined outcome of major macrovascular and microvascular
events, primarily as a consequence of a 21% relative reduction in
nephropathy."
This 2008 report from the New England Journal of Medicine was
cited 69 times in current journal articles
indexed by Clarivate during May-June 2009. Only one other medicine
paper published in the last two years, aside from reviews, collected a
higher citation total during that two-month period. Prior to the most
recent bimonthly count, citations to the paper have accrued as follows:
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