267
The Role of Diabetes, Obesity, and Metabolic
Syndrome in Stroke
Xian Nan Tang, MD, PhD1 David S. Liebeskind, MD1
1 Department of Neurology, UCLA Stroke Center, Geffen School of
Medicine at UCLA, Los Angeles, California
2 Division of Stroke and Neurocritical Care, Keck School of Medicine,
University of Southern California, Los Angeles, California
3 Department of Neurology, Rancho Los Amigos National
Rehabilitation Center, Downey, California
Semin Neurol 2017;37:267–273.
Abstract The prevalence of obesity, diabetes, and metabolic syndrome has increased globally.
Keywords These epidemiologic changes are likely responsible for a rise in stroke incidence among
► diabetes young adults, despite declining stroke incidence rates in the elderly. In this review, the
► obesity authors summarize the current understanding of the epidemiology and pathophysiol-
► metabolic syndrome ogy of stroke associated with obesity, diabetes, and metabolic syndrome.
► stroke prevention
In the United States, stroke was the third leading cause of
death about a decade ago, and is now the fifth most common
cause of death, following diseases of the heart, cancer,
chronic lower respiratory diseases, and unintentional inju-
ries/accidents.1 In addition, data from Brain Attack Surveil-
lance in Corpus Christi Study, the Framingham Heart Study,
Medicare beneficiaries, the Greater Cincinnati Northern
Kentucky Stroke Study, and Atherosclerosis Risk in Commu-
nities Study suggest that ischemic stroke incidence has
declined in the United States, particularly in individuals
over the age of 60 years.2–7 Despite these improvements in
stroke incidence and mortality, epidemiologic studies sug-
gest that stroke incidence has increased among younger
individuals,8–10 and from 2010 to 2030, the estimated total
direct medical costs due to stroke is projected to escalate
from $273 billion in 2010 to $818 billion in 2030 in the
United States alone.11 Potential contributors to the increased
burden of stroke in younger individuals likely include the
burgeoning obesity epidemic and the constellation of risk
factors associated with obesity, namely, insulin resistance,
diabetes, hypertension, and dyslipidemia. A recent analysis
of data from the National Inpatient Sample revealed that
among adults aged 18 to 64 years hospitalized with acute
stroke in the United States, the prevalence of hypertension,
lipid disorders, diabetes, and obesity increased significantly
from 2003/2004 to 2011/2012 in both men and women.12
Issue Theme Stroke Prevention; Guest
Editor, Amytis Towfighi, MD
Amytis Towfighi, MD2,3
Address for correspondence Amytis Towfighi, MD, Rancho Los
Amigos National Rehabilitation Center, 7601 E. Imperial Highway,
HB 145, Downey, CA 90242 (e-mail: towfighi@usc.edu).
Downloaded by: Universite Laval. Copyrighted material.
Obesity, diabetes, and a cluster of related factors termed
metabolic syndrome (i.e., abdominal obesity, hypertension,
low high-density lipoprotein (HDL) cholesterol, high trigly-
cerides, and insulin resistance) are recognized risk factors for
stroke. Obesity is notoriously difficult to treat and research
has begun to elucidate the humoral and behavioral mechan-
isms that sustain body weight and limit the losses achievable
with dietary modification.13–15 Here we will (1) summarize
the data describing the association between obesity, dia-
betes, and metabolic syndrome, and stroke; and (2) identify
current recommendations with respect to primary and
secondary stroke prevention.
Epidemiology of Obesity, Diabetes, and
Metabolic Syndrome
The prevalence of overweight and obesity has increased world-
wide over the last quarter of a century. According to the Global
Burden of Disease Study, which included 1,769 country-years
of data and 19,244 country-year-age-sex data points from 183
countries, the proportion of adults with a body mass index
(BMI) of 25 kg/m2 or greater increased from 28.8% in 1980 to
36.9% in 2013 for men, and from 29.8% to 38.0% for women.16
The increases were observed in both developed and develop-
ing countries with key sex differences. In developed countries,
more men than women were overweight and obese, whereas
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268 The Role of Diabetes, Obesity, and Metabolic Syndrome in Stroke
in developing countries, overweight and obesity was more
prevalent in women than in men, and this association per-
sisted over time.16 Trends in prevalence of adult age-standar-
dized obesity over successive cohorts in developed and
developing countries showed that successive cohorts seemed
to be gaining weight at all ages, including childhood and
adolescence, with most rapid gains between the ages of 20
and 40 years. There have been substantial increases in obesity
prevalence among children and adolescents in developed
countries, with 23.8% of boys and 22.6% of girls overweight
or obese in 2013. The prevalence of overweight status and
obesity has also risen in children and adolescents in develop-
ing countries, from 8.1% to 12.9% in 2013 for boys and from
8.4% to 13.4% in girls.16
In adults, the estimated prevalence of obesity exceeded
50% in men in Tonga and women in Kuwait, Kiribati, the
Federated States of Micronesia, Libya, Qatar, Tonga, and
Samoa. In North America, the United States stood out for
its high prevalence of obesity; in 2013, roughly a third of men
(31·6% [30·0–33·4]) and women (33·9% [31·8–35·7]) were
obese, figures similar to the prevalence identified in the U.S.
National Health and Nutrition Examination Surveys (2011–
2014), which identified a prevalence of 36% (38% in women
and 34% in men). Among youth 2–19 years of age, the
prevalence of obesity in the United States was 17% in
2011–2014. Obesity prevalence varied by gender, race/eth-
nicity, and socioeconomic status.
Individuals with stroke similarly have a higher prevalence
of obesity and its associated risk factors. In an analysis of
363,339 hospitalizations from 2003 to 2004 and 421,815
hospitalizations from 2011 to 2012 in the National Inpatient
Sample, the prevalence of stroke risk factors among those
hospitalized for acute ischemic stroke increased from 2003/
2004 through 2011/ 2012 for both men and women aged 18
to 64 years (range of absolute increase: hypertension, 4–11%;
lipid disorders, 12–21%; diabetes, 4–7%; and obesity, 4–
9%).12 The prevalence of having three to five risk factors
increased from 2003/2004 through 2011/2012 (men: from
9–16% at 18–34 years, 19–35% at 35–44 years, 24–44% at 45–
54 years, and 26–46% at 55–64 years; women: 6–13% at 18–
34 years, 15–32% at 35–44 years, 25–44% at 45–54 years, and
27–48% at 55–65 years; p for trend < 0.001).12
A Nationwide Inpatient Sample analysis revealed that
from 1997 to 2006, the absolute number of acute ischemic
stroke hospitalizations declined by 17%; however, the abso-
lute number of acute ischemic stroke hospitalizations with
comorbid diabetes rose by 27% (from 97,577 [20%] to 124,244
[30%]). The rise in comorbid diabetes was more pronounced
in individuals who were younger, Black or “other” race, had
Medicaid insurance, or were admitted to hospitals located in
the South. Factors independently associated with higher
odds of diabetes in acute ischemic stroke patients were Black
or “other” (vs. White) race, congestive heart failure, periph-
eral vascular disease, and history of myocardial infarction,
renal disease, or hypertension.18
Metabolic syndrome is highly prevalent in the United
States; in fact, one out of five adults is affected by metabolic
syndrome.19 An assessment of adults who participated in the
Seminars in Neurology Vol. 37 No. 3/2017
Tang et al.
U.S. National Health and Nutrition Examination Surveys
1999/2010 (n ¼ 12,502) revealed that 61.2% of individuals
with self-reported stroke met criteria for metabolic syn-
drome on exam.20
Diabetes and Risk of Stroke
Diabetes increases the risk for stroke, with a possible differ-
ential impact by race/ethnicity and sex. The Greater Cincinnati
Northern Kentucky Stroke Study showed that the risk ratio for
ischemic stroke in Blacks < 65 years of age was 5.2 compared
with 12.0 for Whites. Overall, ischemic stroke patients with
diabetes were younger, more likely to be Black, and more likely
to have hypertension, myocardial infarction, and high choles-
terol than nondiabetic patients.4 A systematic review of 64
cohort studies representing 775,385 individuals and 12,539
strokes revealed that the pooled maximum adjusted relative
risk (RR) of stroke associated with diabetes was 2.28 (95% CI,
1.93–2.69) in women and 1.83 (95% CI, 1.60–2.08) in men.
Compared with men with diabetes, women with diabetes had
a 27% greater RR for stroke when baseline differences in other
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major cardiovascular risk factors were considered (pooled
ratio of RR, 1.27, 95% CI, 1.10–1.46; 12 ¼ 0%).21
Prediabetes may also be associated with a higher RR of
stroke: a meta-analysis of 15 prospective cohort studies includ-
ing 760,925 participants revealed that when prediabetes was
defined as a fasting glucose of 110–125 mg/dL (five studies), the
adjusted RR for stroke was 1.21 (95% CI, 1.02–1.44; p ¼ 0.03).22
Diabetes is also a risk factor for stroke recurrence; a meta-
analysis of 18 studies (n ¼ 43,899 participants with prior
stroke) revealed a higher stroke recurrence in individuals
with diabetes compared with those without (HR, 1.45; 95%
CI, 1.32–1.59).23
Pathophysiologic Effects of Diabetes
The mechanisms by which impaired glucose tolerance and
diabetes result in stroke are multifactorial. Diabetes can
cause both microvascular and macrovascular complications,
culminating in strokes of different subtypes. Postprandial
hyperglycemia contributes to vascular damage by several
mechanisms such as endothelial dysfunction, atherosclero-
sis, oxidative stress, inflammation, and hypercoagulability.24
Insulin resistance has been linked to impaired blood flow,
micro- and macroangiopathy, hypertension, and endothelial
cell dysfunction.25 Glucose metabolism is closely associated
with the secretion and effectiveness of insulin, body fat, and
ininfflammation.26 In addition, diabetes may cause platelet
dysfunction and subsequent aspirin resistance that limits
effective secondary stroke prevention.27
Pattern of Stroke in Diabetics
Diabetes has been associated with both small vessel disease
and large artery atherosclerosis. In the Lausanne Stroke Reg-
istry (n ¼ 4,064 consecutive patients),28 diabetes was asso-
ciated with higher relative prevalence of subcortical infarction
(odds ratio [OR], 1.34; 95% CI, 1.11–1.62; p ¼ 0.009) and
higher relative frequency of small-vessel (OR, 1.78; 95% CI,
1.31–3.82; p ¼ 0.012) and large-artery disease (OR, 2.02; 95%
 The Role of Diabetes, Obesity, and Metabolic Syndrome in Stroke
CI, 1.31–2.02; p ¼ 0.002) compared with stroke survivors
without diabetes. A small Chinese study,29 which enrolled
199 patients, found that brainstem stroke due to large artery
disease significantly associated to diabetes, with an OR of 2.84
(p ¼ 0.003).
Hyperglycemia and Acute Stroke Outcomes
Hyperglycemia in the setting of acute stroke is common,
particularly among diabetic patients, and is associated with
poorer outcomes. Several studies have shown admission
blood glucose is elevated in > 40% of patients with acute
ischemic stroke.30 Hyperglycemia is often due to a stress
response, in both diabetic and nondiabetic patients. A pro-
spective cohort study (n ¼ 482 hospitalized stroke patients),
including 32.2% with diabetes, compared in-hospital mor-
tality and modified Rankin Score (mRS) at discharge between
diabetic and nondiabetic groups, and found that diabetes did
not affect ischemic stroke severity, but was independently
associated with a worse functional outcome at discharge.31
A systematic review and meta-analysis of 26 studies
revealed that after ischemic stroke, admission glucose level
6.1 to 7.0 mmol/L (110–26 mg/dL) was associated with
increased risk of in-hospital or 30-day mortality in nondia-
betic patients only (RR, 3.28; 95% CI, 2.32–4.64).32 After
hemorrhagic stroke, admission hyperglycemia was not asso-
ciated with higher mortality in either diabetic or nondiabetic
patients.32 Individuals studies, however, have shown that
hyperglycemia at and after admission for hemorrhagic stroke
was associated with worse outcomes at discharge,
1 month,33 and 3 months.34 In addition, prestroke hypergly-
cemia has been associated with a larger volume of hematoma
and poor outcome after intracerebral hemorrhage.35
Hyperglycemia appears to have an impact on outcomes
after thrombolytic administration. Among stroke patients
treated with intravenous recombinant tissue plasminogen
activator (IVrtPA), hyperglycemia has been associated with
symptomatic intracerebral hemorrhage and worse clinical
outcomes.30 A rat model showed that hyperglycemia during
rtPA infusion resulted in diffusely increased blood–brain
barrier permeability in the ischemic territory, increased
superoxide formation in the brain parenchyma and vascu-
lature during reperfusion, and a three- to fivefold increase in
hemorrhagic transformation volumes.36 In the multicenter
Canadian Alteplase for Stroke Effectiveness Study (CASES),
among the 1,098 patients who received IVrtPA, 296 (27%)
had admission hyperglycemia, including 18% of those with-
out diabetes and 70% of those with diabetes. Hyperglycemia
at admission was independently associated with increased
mortality and symptomatic intracranial hemorrhage, as well
as poor functional status at 90 days.37
The current American Heart Association Guidelines for
Acute Ischemic Stroke recommend maintaining blood glu-
cose levels in a range of 140 to 180 mg/dL and close
monitoring to prevent hypoglycemia (Class IIa; Level of
Evidence C).30 The Stroke Hyperglycemia Insulin Network
Effort (SHINE) Trial is an ongoing, multicenter randomized
controlled trial (RCT) of 1,400 hyperglycemic patients who
receive either standard sliding scale subcutaneous insulin
Tang et al. 269
(blood glucose range 80–179 mg/dL, 4·44–9·93 mmol/L) or
continuous IV insulin (target blood glucose 80–130 mg/dL,
4·44–7·21 mmol/L) for up to 72 hours, starting within
12 hours of stroke symptom onset. The primary outcome
is a baseline severity adjusted 90-day mRS, and the primary
safety outcome is the rate of severe hypoglycemia.38
Diabetes and Stroke Outcomes
A prospective cohort study (n ¼ 482 hospitalized stroke
patients), including 32.2% with diabetes, compared in-hos-
pital mortality and mRS at discharge between diabetic and
nondiabetic groups, and found that diabetes did not affect
ischemic stroke severity, but was independently associated
with a worse functional outcome at discharge.31
Primary and Secondary Prevention of Stroke in
Individuals with Insulin Resistance or Diabetes
The Insulin Resistance Intervention after Stroke Trial was a
multicenter RCT that randomized 3,876 patients with recent
ischemic stroke or TIA and insulin resistance (on the basis of
a score of more than 3.0 on the homeostasis model assess-
Downloaded by: Universite Laval. Copyrighted material.
ment of insulin resistance index) to receive either pioglita-
zone (target dose 45 mg daily) or placebo.39 By 4.8 years, a
primary outcome of fatal or nonfatal stroke or myocardial
infarction had occurred in 175 of 1,939 patients (9.0%) in the
pioglitazone group and in 228 of 1937 (11.8%) in the placebo
group (HR in the pioglitazone group, 0.76; 95% CI, 0.62–0.93;
p ¼ 0.007).39 Diabetes developed in 73 patients (3.8%) and
149 patients (7.7%), respectively, (HR, 0.48; 95% CI, 0.33–
0.69; p < 0.001). There was a higher frequency of weight
gain, edema, and bone fracture requiring surgery or hospi-
talization in the treatment arm.40
Evidence supports traditional approaches such as mini-
mizing saturated fat intake, weight control, and remaining
physically active for primary prevention of stroke in dia-
betics. Treating comorbidities, such as hypertension and
hyperlipidemia, is also important for primary prevention
of stroke. The 2014 American Heart Association (AHA) guide-
line for primary stroke prevention specifically recom-
mended: “Treatment of adults with diabetes mellitus with
a statin, especially those with additional risk factors…to
lower the risk of first stroke (Class I; Level of Evidence A).”41
A multicenter, prospective RCT in Japan randomized 2,539
patients with type 2 diabetes without a history of athero-
sclerotic disease to a low-dose aspirin group (81 or 100 mg/
day) or a control group and followed them for a median
follow-up of 4.37 years. There were no significant differences
in the primary end points of atherosclerotic events, including
fatal or nonfatal ischemic heart disease, fatal or nonfatal
stroke, and peripheral arterial disease; however, the com-
bined end point of fatal coronary events and fatal cerebro-
vascular events occurred in 1 patient (stroke) in the aspirin
group and 10 patients (5 fatal myocardial infarctions and 5
fatal strokes) in the nonaspirin group (HR, 0.10; 95% CI, 0.01–
0.79; p ¼ .0037).42 According to the 2014 AHA guidelines:
“The usefulness of aspirin for primary stroke prevention for
patients with diabetes mellitus but low 10-year risk of CVD is
unclear (Class IIb; Level of Evidence B).”41
Seminars in Neurology Vol. 37 No. 3/2017
270 The Role of Diabetes, Obesity, and Metabolic Syndrome in Stroke
For secondary stroke prevention, the American Diabetes
Association (ADA) recommends the use of aspirin as a pre-
vention measure in diabetic patients with atherosclerotic
disease.43 Aspirin, however, has inadequate antithrombotic
effect in diabetics compared with those without diabetes.44 A
randomized controlled study showed aspirin had no signifi-
cant dose-dependent effect on markers of vascular inflam-
mation, oxidative stress, insulin resistance, and endothelial
function when given to type 2 diabetes over a 2-week
period.45 The Clopidogrel versus Aspirin in Patients at Risk
of Ischemic Events (CAPRIE) Trial compared the efficacy of
clopidogrel (75 mg daily) versus aspirin (325 mg daily) for
secondary prevention (primary endpoint: myocardial infarc-
tion, stroke, and death) in a high-risk population
(n ¼ 19,185) consisting of patients with a history of recent
myocardial infarction, recent ischemic stroke, or established
peripheral artery disease. Clopidogrel showed higher effi-
cacy in terms of secondary prevention compared with as-
pirin (15.6% vs. 17.7%; p ¼ 0.042) in diabetic patients.46
Nevertheless, the ADA and AHA have not officially endorsed
the use of clopidogrel in the setting of secondary prevention
of stroke in diabetic patients.
Blood pressure (BP) lowering reduces the risk of stroke in
diabetic patients. A meta-analysis of 40 RCTs of BP lowering
among 100,354 participants with diabetes revealed a lower
risk of stroke (combined RR, 0.73; 95% CI, 0.64–0.83; absolute
risk reduction [ARR], 4.06; 95% CI, 2.53–5.40).47 A subsequent
meta-analysis of 28 RCTs involving 96,765 participants with
diabetes revealed that a decrease in systolic BP (SBP) by 10 mm
Hg was associated with lower risk of stroke (RR, 0.74; 95% CI,
0.66–0.83).48 Significant interactions were observed, with
lower RRs (RR, 0.71; 95% CI, 0.63–0.80) observed among trials
with mean baseline SBP  140 mm Hg and no significant
associations among trials with baseline SBP < 140 mm Hg.
Finally, the ADA encourages clinicians to employ a patient-
centered approach to selection of medications after metfor-
min in diabetics, considering the costs, side-effect profiles,
and target A1C reduction.41 Intensive hyperglycemia treat-
ment may double the risk of hypoglycemia. In a meta-
analysis of four RCTs including 27,544 diabetics, those ran-
domized to intensive glucose control did not have a reduc-
tion in stroke risk compared with those who received
conventional glucose control; however, there was a 14%
reduction in nonfatal myocardial infarction (incident rate
ratio, 0.86; 95% CI, 0.77–0.97).49
Obesity and Stroke Risk
In a recent meta-analysis that included eight cohort studies,
the pooled adjusted RR of stroke was 1.36 (95% CI, 1.28–1.44)
for overweight individuals and 1.81 (95% CI, 1.45–2.25) for
obese individuals.50 For every 1 unit increase in BMI (7
pounds for a human of average height), the risk for ischemic
stroke increases 5% and the risk increases linearly starting
at a BMI of 20 kg/m2.15,51,52 Measures of abdominal obesity
such as waist-to-hip ratio or waist circumference are inde-
pendently associated with an increased risk of cerebrovas-
cular events.53–58
Seminars in Neurology Vol. 37 No. 3/2017
Tang et al.
Obesity and Outcomes after Stroke: Stroke
Recurrence and Mortality
Although overweight and obesity are associated with stroke
incidence, the associations between obesity and stroke re-
currence have been inconsistent. A recent meta-analysis
including 54,372 patients from five studies59–63 showed
that compared with normal weight patients, the pooled
estimates of RR for recurrent stroke events were 1.03 (95%
CI, 0.81–1.32; p ¼ 0.797) in underweight patients, 0.96 (95%
CI, 0.90–1.04; p ¼ 0.315) in overweight patients, and 0.89
(95% CI, 0.77–1.02, p ¼ 0.096) in obese patients.64 In addi-
tion, a linear relationship between BMI and recurrent stroke
events was observed, with a significant trend p for trend
¼ 0.02, and limited heterogeneity (I2 ¼ 0.0%, p for hetero-
geneity ¼ 0.90): the higher the BMI, the lower the risk of
recurrent TIA/stroke.
In addition, studies regarding the association between
obesity and mortality after stroke have been variable. A
prospective study of stroke patients admitted over a period
of 16 years (1993–2008; n ¼ 2,913) revealed higher early
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(first week) survival in obese (96.4%; 95% CI, 94.8–97.9%) and
overweight patients (92.8%; 95% CI, 91.2–94.4%) compared
with normal-weight patients (90.2%; 95% CI, 88.4–92.0%).
Similarly, 10-year survival was higher at 52.5% (95% CI, 46.4–
58.6%) in obese and 47.4% (95% CI, 43.5–51.3%) in overweight
versus 41.5% (95% CI, 39.7–45.0%) in normal-weight patients
(log-rank test ¼ 17.7; p < 0.0001). Overweight (HR, 0.82;
95% CI, 0.71–0.94) and obese patients (HR, 0.71; 95% CI, 0.59–
0.86) had a significantly lower risk of 10-year mortality
compared with normal-weight patients after adjusting for
all confounding variables.59 An analysis of a Danish quality-
control registry from 2000 to 2010 (n ¼ 45,615 acute first-
ever stroke patients with information on BMI in 29,326)
showed that mortality was significantly lower in overweight
(HR, 0.72; 95% CI, 0.68–0.78) and obese (HR, 0.80; 95% CI,
0.73–0.88) patients while significantly higher in under-
weight patients (HR, 1.66; 95% CI,1.49–1.84) compared
with normal-weight patients.62 On the other hand, data
from 5,512 individuals who died of stroke in whom BMI
was available from the Danish Stroke Register and Danish
Registry of Causes of Death,65 there was no difference in the
risk for death by stroke in the first month among patients
who were normal weight (reference), overweight (HR, 0.96;
95% CI, 0.88–1.04), and obese (HR, 1.0; 95% CI, 0.88–1.13).65
Pathophysiologic Effects of Obesity
Obesity contributes to stroke risk via various pathophysiolo-
gical mechanisms. First, obesity is associated with various
vascular risk factors including hypertension, dyslipidemia
(elevated triglycerides and low HDL-cholesterol), diabetes,
obstructive sleep apnea, and atrial fibrillation. Second, obesity
itself leads to a prothrombotic, inflammatory state contribut-
ing to accelerated atherosclerosis.15 As individuals gain
weight, adipose undergoes hyperplasia, remodeling, and in-
filtration with inflammatory cells.15 In the setting of inflam-
mation, C reactive protein is upregulated, free fatty acids are
released, adiponectin is reduced, insulin resistance and
 The Role of Diabetes, Obesity, and Metabolic Syndrome in Stroke
subsequent hyperglycemia develop, and the threshold for
atherosclerotic plaque rupture is reduced.15 During adipose
tissue metabolism, byproducts such as nonesterified fatty
acids, cytokines, and adiponectin may affect blood glucose
levels and insulin effectiveness. Thus excess body adiposity
may contribute to stroke risk via several mechanisms, includ-
ing hypertension, dyslipidemia, insulin resistance, inflamma-
tion, endothelial damage, and hypercoagulability.15
Effect of Weight Loss on Vascular Disease
Although no studies have evaluated the effects of intentional
weight loss on outcomes after stroke, weight loss has been
associated with improvements in BP, glucose, triglycerides,
HDL, insulin sensitivity, and markers of inflammation in
individuals without stroke.66–70
Obesity and Stroke Prevention
The finding that obese individuals with certain conditions
have better outcomes than their normal-weight counter-
parts is called the “obesity paradox.” The association does
not, however, imply causality. An epidemiologic association
between obesity and improved survival could reflect a
survival bias (e.g., obese patients who survived until their
events could be relatively healthy individuals or have meta-
bolically benign obesity).15 Given the lack of understanding
of the significance of this obesity paradox, and known
detrimental effects of obesity on vascular risk factors, the
U.S. Preventive Services Task Force recommends screening
for obesity and referring obese adults to intensive multi-
component behavioral interventions.
The U.S. Preventive Services Task Force performed a sys-
tematic review and meta-analysis of behavioral interventions
(38 trials, n ¼ 13,495), the use of orlistat (18 trials, n ¼ 11,256)
or metformin (3 trials, n ¼ 2,652) for weight loss or weight
maintenance in adults in the general population71 and found
that behavioral treatment resulted in an average weight loss of
3.0 kg more in intervention participants compared with con-
trols, with greater weight loss in trials with more treatment
sessions (4–7 kg lost in the intervention group in trials with
11–26 treatment sessions in the first year). Orlistat resulted in
even greater weight loss (generally 6–9 kg total). Metformin
trials were heterogeneous, but one large, good-quality trial
showed a weight loss of 2.3 kg more in the intervention group.
Weight loss treatment was associated with a reduction in
diabetes incidence in two large, good-quality behavioral-
based trials of diabetes prevention. Behavioral-based treat-
ment showed small positive effects on BP. Orlistat improved BP
and lowered low-density lipoprotein cholesterol and plasma
glucose (in patients with diabetes) compared with placebo.71
Metformin did not improve lipid levels or BP, but reduced the
incidence of diabetes.71
In individuals with stroke, AHA secondary stroke guidelines
state that “given the demonstrated beneficial effects of weight
loss on cardiovascular risk factors, the usefulness of weight loss
among patients with a recent TIA or ischemic stroke and
obesity is uncertain (Class IIb; Level of Evidence C).”41
Tang et al. 271
Metabolic Syndrome and Stroke
Metabolic syndrome, a constellation of insulin resistance,
abdominal obesity, hypertension, and dyslipidemia, is asso-
ciated with stroke.26 In a prospective cohort study of 5,398
patients > 35 years of age followed for 10 years, 2,021 (37.4%)
met criteria for metabolic syndrome. Stroke incidence rates for
those with and without metabolic syndrome were 2.6% and
1.1%, respectively (p ¼ 0.026).72 A retrospective study of 1,361
outpatients with minor stroke showed that individuals with
metabolic syndrome had more frequent subsequent vascular
events than those without metabolic syndrome.73 On the other
hand, a prospective study of 1,087 individuals with mild-to-
moderate ischemic stroke, followed for 5 years, showed that
the risk of recurrent stroke in the absence of diabetes was
similar to those without metabolic syndrome or diabetes.74
The primary goal of clinical management of metabolic syn-
drome is to reduce the atherogenic risk factors. At this time,
there are no specific guidelines to treat metabolic syndrome
per se in stroke survivors; therefore, treatment is aimed at
control of individual vascular factors.
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Conclusions
Diabetes, obesity, and metabolic syndrome prevalence have
increased worldwide, despite overall improvements in stroke
incidence, mortality, and outcomes. Studies are needed to
optimize strategies for leading healthier lifestyles and to im-
plement interventions aimed at preparing health care systems
to ensure evidence-based care to curb these epidemics.
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