Tight Glycemic Control Reduces Complications in AMI setting

1. TIGHT GLYCEMIC CONTROL
REDUCES HEART
INFLAMMATION AND
REMODELING DURING ACUTE
MYOCARDIAL INFARCTION IN
HYPERGLYCEMIC PATIENTS
http://www.cardiosource.com/pops/jaccjump.asp
?vol=53&issue=16&page=1425&journal=JACC

2. Methods
Eighty-eight patients with first acute

myocardial infarction (AMI) undergoing bypass
surgery were studied: 38 normoglycemic
patients served as the control group;
hyperglycemic patients (glucose = 140 mg/dl)
were randomized to intensive glycemic control
(IGC) (n = 25; glucose 80-140 mg/dl) or
conventional glycemic control (CGC) (n = 25;
glucose 180-200 mg/dl) for almost 3 days
before surgery, with insulin infusion followed
by subcutaneous insulin treatment

3. Echocardiographic parameters were

investigated at admission and after treatment
period.
During surgery, oxidative stress

(nitrotyrosine, superoxide anion [O2–]
production, inducible nitric oxide synthase
[iNOS]), inflammation (nuclear factor kappa B
[NFκB], tumor necrosis factor [TNF]-α, and
apoptosis (caspase-3) were analyzed in
biopsy specimens taken from the peri-infarcted
area.

4. Results
Compared with normoglycemic

patients, hyperglycemic patients had higher
myocardial performance index (MPI) (p <
0.05), reduced ejection fraction (p <
0.05), more nitrotyrosine, iNOS, and O2–
production, more macrophages, T-
lymphocytes, and HLA-DR cells, and more
NFκB-activity, TNF-α, and caspase-3 levels (p
< 0.01) in peri-infarcted specimens.

5. After the treatment period, plasma glucose

reduction was greater in the IGC than in the
CGC group (p < 0.001). Compared with IGC
patients, CGC patients had higher MPI (p <
0.02), lower ejection fraction (p < 0.05), and
more markers of oxidative
stress, inflammation, and apoptosis (p < 0.01)
in peri-infarcted specimens.

6. Conclusions
Tight glycemic control, by reducing oxidative

stress and inflammation, might reduce
apoptosis in peri-infarcted areas and
remodeling in AMI patients.

7. Perspective
This mechanistic study suggests that tight

glycemic control during the ischemic insult
may be associated with reduction of early
post-infarction remodeling. The study, while
promising, needs to be validated in larger
cohorts, and the clinical implications of the
reduction in remodeling needs to be defined..

8. The NICE-SUGAR study recently suggested

that intensively lowering blood glucose to a
target of 81-108 mg/dl does not benefit
critically ill patients and increase their risk of
dying.

9. For now, it seems prudent to follow the

American Heart Association Scientific
Statement recommendations on
hyperglycemia and acute coronary syndrome
(ACS) (Circulation 2008;117:1610-9), which
states that in patients admitted to an intensive
care unit (ICU) with ACS, approximation of
normoglycemia appears to be a reasonable
goal (suggested range for plasma glucose 90-
140 mg/dl), as long as hypoglycemia is
avoided.

10. In patients hospitalized in the non-ICU

setting, efforts should be directed at
maintaining plasma glucose levels <180 mg/dl
with subcutaneous insulin regimens

11. Relationship Between Spontaneous and Iatrogenic
Hypoglycemia and Mortality in Patients Hospitalized With
Acute Myocardial Infarction
JAMA Vol. 301 No. 15, April 15, 2009
Retrospective cohort study using data from

Health Facts, a contemporary database of
patients hospitalized across the United States
in 40 hospitals between January 1, 2000, and
December 31, 2005.

12. Of all the patients in the database, 7820

patients were hospitalized with AMI andwere
hyperglycemic on admission (glucose
level 140 mg/dL).
Patients were stratified based on whether they

developed a hypoglycemic event (random
glucose level <60 mg/dL) during
subsequent hospitalization.
Logistic regression models were used to

evaluate the association between
hypoglycemia and in-hospital mortality within
subgroups of patients who were and were not

13. Among patients treated or not treated with

insulin, those with hypoglycemia were older
and had more comorbidity. Hypoglycemia was
associated with increased mortality in patients
not treated with insulin (18.4% [25/136]
mortality in patients with hypoglycemia vs.
9.2% [425/4,639] in those without
hypoglycemia; p < 0.001),

14. Insulin Induced Hypoglycemia
does not increase mortality in AMI
setting
but not in those treated with insulin (10.4%

[36/346] mortality in patients with
hypoglycemia vs. 10.2% [276/2,699] in those
without hypoglycemia; p = 0.92).

15. After multivariable adjustment, there was a

significant interaction between hypoglycemia
and insulin therapy (p value for interaction =
0.01). Hypoglycemia was a predictor of higher
mortality in patients who were not treated with
insulin (odds ratio, 2.32 [95% confidence
interval, 1.31-4.12] vs. patients without
hypoglycemia), but not in patients treated with
insulin (odds ratio, 0.92 [95% confidence
interval, 0.58-1.45] vs. patients without
hypoglycemia).

16. Conclusions
While hypoglycemia was associated with

increased mortality in patients with AMI, this
risk was confined to patients who developed
hypoglycemia spontaneously.
In contrast, iatrogenic hypoglycemia after

insulin therapy was not associated with
higher mortality risk.