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(Stroke. 1996;27:63-68.)
© 1996 American Heart Association, Inc.
Articles |
Predictors of Stroke in Middle-Aged Patients With Non–Insulin-Dependent Diabetes
From the Department of Medicine, Kuopio University Hospital, Kuopio (S.L., K.P., M.L.), and the Department of Medicine, Turku University Central Hospital, and The Social Insurance Institution, Turku (T.R.), Finland.
Correspondence to Markku Laakso, MD, Department of Medicine, Kuopio University Hospital, SF-70210 Kuopio, Finland.
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Abstract |
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 Top Abstract IntroductionSubjects and Methods Results Discussion References |
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Background and Purpose The risk of stroke is known to be markedly elevated in patients with non–insulin-dependent diabetes mellitus (NIDDM), but the information on risk factors predicting stroke events in middle-aged NIDDM patients is limited. Therefore, we evaluated the significance of different cardiovascular risk factors with respect to the incidence of stroke in middle-aged NIDDM patients.
Methods Levels of cardiovascular risk factors were determined at baseline in 1059 NIDDM patients (581 men, 478 women) and 1373 nondiabetic control subjects (638 men, 735 women), aged from 45 to 64 years, in eastern and western Finland. These patients were followed up for 7 years with respect to stroke events.
Results Altogether, 34 NIDDM patients (13 men, 21 women) and 5 nondiabetic subjects (4 men, 1 woman) died from stroke, and 125 NIDDM patients (61 men, 64 women) and 30 (18 men, 12 women) nondiabetic subjects had a fatal or nonfatal stroke. The risk of stroke in NIDDM men was about threefold and in NIDDM women fivefold higher than that in corresponding nondiabetic subjects. Previous history of stroke increased the risk of a new stroke event by threefold. Patients with hyperglycemia (plasma glucose >13.4 mmol/L) and high hemoglobin A1 (>10.7%) had about a twofold higher risk of stroke than patients with better glycemic control. Low levels of high-density lipoprotein cholesterol (<0.90 mmol/L), high levels of total triglyceride (>2.30 mmol/L), and the presence of hypertension were associated with a twofold increase in the risk of stroke mortality or morbidity.
Conclusions Our prospective population-based study gives evidence that previous history of stroke, hypertension, hyperglycemia, and dyslipidemia are strong predictors of stroke in middle-aged patients with NIDDM.
Key Words: diabetes mellitus • glucose • mortality • risk factors
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Introduction |
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TopAbstractIntroductionSubjects and Methods Results Discussion References |
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Several studies have indicated that NIDDM increases the risk of ischemic stroke.1 In the Framingham Study, the risk of stroke was 2.6-fold higher in men with NIDDM and 3.8-fold higher in women with NIDDM than in nondiabetic subjects of the corresponding sex.2 Furthermore, diabetic patients have more severe strokes and a higher mortality rate after stroke.3
Hypertension is the strongest predictor of stroke in nondiabetic subjects as well as in patients with NIDDM.2 4 5 Other established risk factors for ischemic stroke include age, male sex, smoking, and atrial fibrillation.6 7 Moreover, factors related to the diabetic state itself (eg, hyperglycemia) might be important with respect to the risk of stroke,8 9 but our knowledge on that subject is still limited.1 Furthermore, no information is available on dyslipidemia as a predictor of stroke in NIDDM patients.
The aim of this prospective population-based study including large cohorts of NIDDM patients and nondiabetic subjects was to investigate risk factors for stroke morbidity and mortality in patients with NIDDM.
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Subjects and Methods |
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TopAbstractIntroductionSubjects and Methods Results Discussion References |
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Research Design and Methods at the Baseline Study
Patients With NIDDM
All diabetic patients in Finland who need antidiabetic drug therapy receive it free of charge according to the Sickness Insurance Act. The Social Insurance Institution maintains a central register of diabetic subjects receiving drug reimbursement. On the basis of information from this register, we identified all diabetic patients aged 45 to 64 years born and living in the Kuopio University Hospital district (East Finland) and in the Turku University Central Hospital district (West Finland). From this data source, the patient population enrolled in this study consisted of 510 diabetic subjects (253 men, 257 women) from East Finland (participation rate, 83%) and 549 diabetic subjects (328 men, 221 women) from West Finland (participation rate, 79%), as has been previously described in detail.10 Insulin-dependent diabetes was excluded in all insulin-treated NIDDM patients by C peptide measurements. All NIDDM patients included in the final study population had a plasma C peptide concentration of at least 0.20 nmol/L 6 minutes after administration of 1 mg IV glucagon. A cutoff point of 0.20 nmol/L was chosen because postglucagon C peptide values below this limit have been shown to be associated with the occurrence of ketoacidosis in insulin-treated diabetic subjects.11 None of the patients classified as having NIDDM according to the WHO criteria12 and included in the study population had a history of ketoacidosis. Of the 510 NIDDM patients from East Finland, 46 men and 38 women were treated with diet only, 183 men and 175 women with oral hypoglycemic drugs, and 24 men and 44 women with insulin. Of 549 NIDDM patients from West Finland, 46 men and 17 women were treated with diet only, 227 men and 177 women with oral hypoglycemic drugs, and 55 men and 27 women with insulin. The age of diabetic men from East Finland was 56.8±0.3 years, and from West Finland it was 57.2±0.3 years; the age of diabetic women from East Finland was 58.9±0.3 years, and from West Finland it was 58.7±0.3 years.
Nondiabetic Subjects
A
random control-population sample of subjects who were born
in the Kuopio University Central Hospital district (East Finland) or in
the Turku University Central Hospital district (West Finland) and were
living in these areas was taken from the population register containing
all subjects aged 45 to 64 years. The details of formation of these
nondiabetic samples have been published previously.10
Participation rates were 79% in East Finland and 85% in West Finland.
The study population consisted finally of 649 subjects (313 men, 336
women) in East Finland and 724 subjects (325 men, 399 women) in West
Finland. The age of nondiabetic men from East Finland was 53.8±0.3
years, and from West Finland it was 54.5±0.3 years; the age of
nondiabetic women from East Finland was 54.6±0.3 years, and from West
Finland it was 54.0±0.3 years.
Study Program and
Methods at Baseline Examination in
1982-1984
The study program for both diabetic and nondiabetic subjects
was
carried out during one outpatient visit at the Clinical Research Unit
of the University of Kuopio or the Rehabilitation Research Centre of
the Social Insurance Institution in Turku. These methods have been
described previously.10 The visit included an interview on
the history of chest pain symptoms suggestive of coronary heart
disease, smoking, alcohol intake, physical activity, and the use of
drugs. All medical records of those subjects who reported in the
interview that they had been admitted to the hospital on the basis of
chest pain or symptoms suggestive of stroke were reviewed. Review of
the medical records was performed by two of us (M.L. in Kuopio and
T.R. in Turku) after a careful standardization of the methods and after
training sessions among the reviewers. The WHO criteria for verified
definite or possible myocardial infarction based on chest pain
symptoms, electrocardiographic changes, and enzyme determinations were
used in the ascertainment of the diagnosis of previous myocardial
infarction.13 The WHO criteria for verified definite or
possible stroke were used in the ascertainment of the diagnosis of
previous stroke, which was defined as a clinical syndrome consisting of
neurological symptoms persisting for >24 hours.14
Thromboembolic and hemorrhagic strokes, but not subarachnoid
hemorrhage, were included in the diagnosis of stroke.
Blood pressure was measured with a mercury sphygmomanometer with the subject in the sitting position after a 5-minute rest and read to the nearest 2 mm Hg. A subject was classified as having hypertension if he or she was receiving drug treatment for hypertension or if systolic blood pressure was at least 160 mm Hg or diastolic blood pressure at least 95 mm Hg.
Weight and height were measured with the subject in light clothing without shoes. BMI was calculated by weight (kilograms) divided by height squared (meters squared).
Biochemical Methods
All laboratory specimens were drawn after a 12-hour fast at 8
AM. The analyses were performed in duplicate except
for GHbA1. Fasting plasma glucose was determined by the
glucose oxidase method (Boehringer). GHbA1 was
determined by affinity chromatography (Isolab). The
plasma C peptide response to glucagon was assessed according to the
method of Faber and Binder.15 Plasma C peptide was
determined by radioimmunoassay (antiserum M 1230, Novo).16
Serum lipids and lipoproteins were determined from fresh serum samples
drawn after a 12-hour overnight fast. Serum total
cholesterol and triglyceride levels were
assayed by automated enzymatic methods
(Boehringer).17 Serum HDL cholesterol
was determined enzymatically after precipitation of low-density and
very-low-density lipoproteins with dextran
sulfate–MgCl2.18 Urinary protein
concentration was measured by the Coomassie brilliant blue method
(Bio-Rad Laboratories).
Research Design and Methods of Follow-up Study
In 1990, a
postal questionnaire containing questions about
hospitalization because of acute chest pain and symptoms suggestive of
stroke was sent to every surviving participant of the original study
cohort. All medical records of those subjects who had died between
baseline examination and December 31, 1989, or who reported in the
questionnaire that they had been admitted to the hospital because of
symptoms suggestive of stroke between the baseline examination and
December 31, 1989, were reviewed by one of us (S.L.). To ensure
that the data collection was complete, a computerized hospital
discharge register was used to check hospital admissions of all
participants of the baseline study, and in cases of hospitalization for
stroke, medical records were also checked. Copies of death
certificates of those patients who had died were obtained from the
files of the Central Statistical Office of Finland. In the final
classification of the causes of death, hospital records and autopsy
records were used if available. Causes of death were coded
according to the International Classification of Diseases, 9th Revision
(ICD-9).19
WHO criteria for verified and possible stroke used in the ascertainment of a new stroke event were similar to those used in the baseline study, ie, a clinical syndrome consisting of a neurological deficit and persisting >24 hours (nonfatal stroke), without the presence of other diseases that explained the symptoms.14 Causes of death from stroke included ICD-9 codes 431 through 434. Thus, thromboembolic and hemorrhagic stroke, but not subarachnoid hemorrhage, were included in the diagnosis of stroke.
Statistical Methods
Data analyses were conducted with the
SPSSX
and SPSS/PC+ programs (SPSS Inc). The results
for continuous variables are given as mean±SEM and for categorical
variables as percentages. The differences between the groups were
assessed by the 
2 test or Student's
two-tailed t test for independent samples, as
appropriate. Univariate and multiple logistic regression
analyses based on the maximum-likelihood method were used
to investigate the association of cardiovascular risk
factors with the incidence of coronary heart disease events,
and the results are reported with 95% CIs. Mantel-Haenszel's test for
linear association was used to evaluate the association of the tertiles
of serum lipids and lipoproteins, glycemic control, and the duration of
diabetes with the risk of stroke events. Because
triglyceride concentration was not normally distributed, it
was log transformed in all statistical analyses.
Approval of Ethics Committee
This study was approved by the
Ethics Committee of Kuopio
University Central Hospital.
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Results |
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TopAbstractIntroductionSubjects and Methods Results Discussion References |
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During the follow-up, 23 NIDDM patients (7 men, 16 women) and 3 nondiabetic men from East Finland and 11 NIDDM patients (6 men, 5 women) and 2 nondiabetic subjects (1 man, 1 woman) from West Finland died of stroke. Altogether, 68 NIDDM patients (27 men, 41 women) and 16 nondiabetic subjects (10 men, 6 women) from East Finland and 57 NIDDM patients (34 men, 23 women) and 14 nondiabetic subjects (8 men, 6 women) from West Finland had a fatal or nonfatal stroke event.
Diabetic men had a twofold to threefold higher and diabetic women a fivefold higher risk for stroke than corresponding nondiabetic subjects (men: OR, 2.4 [95% CI, 1.2 to 4.9] in East Finland; OR, 3.3 [95% CI, 1.6 to 6.9] in West Finland; women: OR, 5.5 [95% CI, 2.4 to 12.9] in East Finland; OR, 5.4 [95% CI, 2.3 to 12.6] in West Finland). Because none of the nondiabetic women in East Finland died from stroke during follow-up, it was not possible to calculate ORs for this subgroup. The results were essentially similar when subjects with a history of stroke before the baseline study were excluded. Ischemic stroke was the most common cause of stroke in nondiabetic subjects and NIDDM patients in both areas.
All of the following data analyses concern only NIDDM patients because the small number of stroke events in nondiabetic subjects did not allow any further statistical analyses. Furthermore, both study areas were combined in the following analyses because the results were essentially similar in both areas.
Table 1
summarizes baseline characteristics for NIDDM
men and women in relation to stroke events during 7-year follow-up.
NIDDM men with stroke were significantly older and more often had a
history of previous stroke (P<.05) and higher level of
triglycerides (P=.001) and lower level of HDL
cholesterol (P<.05). In addition, NIDDM men
with stroke had higher levels of plasma glucose (P<.01) and
GHbA1 (P=.01) than those without stroke. NIDDM
women with stroke more often had a history of stroke
(P<.001); they were also more often hypertensive
(P<.001) and had higher total serum total
cholesterol (P=.01), total
triglyceride (P<.05), and fasting plasma
glucose (P<.05) levels, as well as a longer duration of
diabetes (P=.01), than NIDDM women without stroke.
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The risk of stroke in NIDDM patients (men and women combined) was
investigated by calculating age- and sex-adjusted ORs for different
cardiovascular risk factors by univariate
logistic regression analysis (Table 2). Cutoff
points for high total (>6.2 mmol/L) and low HDL
cholesterol (<0.90 mmol/L) and high total
triglyceride (>2.30 mmol/L) levels were based on
high-risk category classification of the National
Cholesterol Education Program.20 The cutoff
points for high plasma glucose (>13.4 mmol/L), GHbA1
(>10.7%), and long duration of diabetes (>9 years) were based on the
highest tertile cutoff points for these variables. The cutoff point
of 27 kg/m2 for BMI was used to define obesity. Previous
history of stroke was associated with a threefold increased risk for
stroke. Low HDL cholesterol, high triglyceride
levels, and hypertension were associated with a twofold risk for
stroke. Furthermore, high fasting glucose was associated with an almost
threefold increased risk, and high GHbA1 and a long
duration of diabetes were associated with an almost twofold increased
risk of stroke. High total cholesterol tended to be
associated with stroke, but the association did not reach the
conventional limit of statistical significance (P<.07).
Obesity and smoking were not associated with an increased risk of
stroke.
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Fig 1 reports stroke events in NIDDM patients (men and
women combined) according to different lipid tertiles and factors
related to glycemic control. High serum total cholesterol
(P<.01), low HDL cholesterol
(P<.01), high triglycerides
(P<.001), high plasma glucose (P<.001), high
GHbA1 (P<.001), and long duration of diabetes
(P<.05) increased the risk of stroke. These variables
were risk factors for stroke also when the data were analyzed
separately for men and women.
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Because hyperglycemia was a strong predictor for stroke, we further
investigated whether this association was independent of other
cardiovascular risk factors. Adjustment for age, sex,
area of residence, previous myocardial infarction, previous stroke,
total cholesterol, total triglycerides,
smoking, BMI, hypertension, HDL cholesterol, atrial
fibrillation, and duration of diabetes did not abolish the association
of high plasma glucose with stroke (OR, 2.6; 95% CI, 1.5 to 3.8). We
also analyzed whether the predictive value of serum lipids with
respect to stroke events was modified by the degree of hyperglycemia.
This was done by dividing diabetic patients into two groups on the
basis of the highest tertile of baseline fasting plasma glucose level
>13.4 mmol/L. The cutoff points for high total cholesterol
(>6.20 mmol/L), low HDL cholesterol (<0.90 mmol/L), and
high total triglyceride (>2.30 mmol/L) levels were based
on high-risk category classification of the National
Cholesterol Education Program,20 as mentioned
earlier. Fig 2 demonstrates that high total
cholesterol, low HDL cholesterol, and high
total triglycerides increased the risk for stroke both in
patients with poor metabolic control (plasma glucose >13.4
mmol/L) and in patients with better glycemic control (plasma glucose
13.4 mmol/L). However, when the risk of stroke was evaluated within
each lipid category, hyperglycemia still increased the incidence of
stroke events significantly.
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We also evaluated the incidence of stroke by the mode of treatment. The incidence of stroke mortality or morbidity was 5.4% in patients treated with diet, 11.2% in patients treated with oral hypoglycemic drugs, and 21.3% in patients treated with insulin (P<.001 among the groups). However, after adjustment for age and sex and for variables that reflect the severity of diabetes (fasting plasma glucose, the presence of proteinuria, and diabetic retinopathy) no statistically significant differences were found between insulin-treated patients and patients treated with diet only or with oral hypoglycemic drugs with respect to the incidence of all stroke events.
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Discussion |
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TopAbstractIntroductionSubjects and Methods Results Discussion References |
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Our 7-year follow-up study based on representative cohorts of nondiabetic and diabetic subjects from Finland demonstrated that NIDDM increased the risk of stroke significantly. NIDDM women were about five times more likely to experience a stroke compared with nondiabetic women. The risk of stroke for diabetic men was two to three times higher than that for nondiabetic men. Our study also confirmed the finding that hypertension is a risk factor for stroke in diabetic patients.4 21 22 23
The main finding of the present study was a strong association of
hyperglycemia with stroke in NIDDM patients. In fact, high fasting
plasma glucose was a risk factor for stroke even after adjustment for
other variables. In addition to fasting plasma glucose, glycemic
control was also assessed by GHbA1, which reflects
hyperglycemia during the preceding 2
months.24 25 26 There
was a dose-response relationship between GHbA1 and risk
of stroke (Fig 1
). The duration of diabetes was also an
important risk
factor for stroke events in NIDDM subjects (Table 2). However,
the
effect of the duration of diabetes was a significant predictor of
stroke events only after 9-year duration of disease. The failure of
previous studies to demonstrate an association between stroke risk and
the duration of diabetes may be due to a narrow range of duration of
disease in these studies.
The importance of GHbA1 and the duration of diabetes as predictors of stroke in the present study is in accordance with the recently published study of the predictors of stroke in an elderly Finnish population including a representative cohort of NIDDM subjects aged 65 to 74 years.9 In that study, fasting plasma glucose and GHbA1 were the strongest predictors of stroke in NIDDM subjects, outweighing all classic risk factors for stroke, but the duration of diabetes was also a predictor of stroke independent of the degree of hyperglycemia. These findings, in addition to ours, give convincing evidence that poor metabolic control, reflected by high blood glucose and GHbA1, is a major risk factor for stroke, independent of age.
Poor metabolic control accelerates diabetic microvascular disease, but the importance of hyperglycemia with respect to macrovascular disease in NIDDM is still controversial.1 27 There are several mechanisms by which hyperglycemia causes atherosclerosis. First, hyperglycemia is related to atherogenic lipoprotein changes.8 Second, hyperglycemia is also a procoagulant state. Accelerated production of von Willebrand factor and fibrinogen and decreased formation of prostacyclin in the diabetic state increase thrombosis formation.8 28 29 Hyperglycemia also causes glycosylation of proteins in the artery wall.30
Hypertriglyceridemia is the most common
lipid abnormality in patients with NIDDM. The level of total
cholesterol may be elevated, and HDL
cholesterol is often decreased.8 31 32
Although lipid abnormalities have been shown to be associated with
cerebral atherosclerosis, data on the relationship
between dyslipidemia and stroke are
limited.33 34 In our study, there was a strong
relationship between low HDL cholesterol and stroke in
patients with NIDDM. In previous studies, this association has been
reported only in men.35 36 Moreover, previous studies
have
failed to show a relationship of high serum cholesterol and
triglyceride levels with the risk of stroke in patients
with NIDDM.35 36 In the present study, there was a
dose-response relationship between total cholesterol,
HDL cholesterol, and triglycerides and the risk
of stroke events in NIDDM subjects (Fig 2).
What is the explanation for the association of hypertriglyceridemia, low HDL cholesterol, and the risk for stroke? Impaired fibrinolysis has emerged as a new risk factor for ischemic heart disease. Fibrinolytic activity in blood is regulated mainly by plasma PAI-1.37 Moreover, increased levels of PAI-1 have been demonstrated in patients with NIDDM38 and in patients with coronary heart disease37 39 and stroke.40 Furthermore, triglyceride level has been shown to correlate with PAI-1.41 Although we did not measure PAI-1 activity, impaired fibrinolysis could be one of the mediating factors between dyslipidemia and the risk of stroke.
In conclusion, our study with follow-up for up to 7 years gives evidence that poor glycemic control is a strong risk factor for stroke in patients with NIDDM. Furthermore, previous stroke, hypertension, high cholesterol, high triglycerides, and low HDL cholesterol are important predictors of future risk of stroke in patients with NIDDM. Our results imply that effective treatment of hyperglycemia, hypertension, and dyslipidemia may help to prevent stroke in patients with NIDDM.
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Selected Abbreviations and Acronyms |
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Acknowledgments |
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This study was supported by grants from the Aarne and Aili Turunen Foundation and the Finnish Heart Research Foundation.
Received June 19, 1995; revision received October 2, 1995; accepted October 2, 1995.
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 M. J. Fowler Microvascular and Macrovascular Complications of Diabetes Clin. Diabetes, April 1, 2008; 26(2): 77 - 82. [Full Text] [PDF]
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 I. Protopsaltis, P. Korantzopoulos, H. J. Milionis, A. Koutsovasilis, G. K. Nikolopoulos, E. Dimou, S. Kokkoris, P. Brestas, M. S. Elisaf, and A. Melidonis Metabolic Syndrome and Its Components as Predictors of Ischemic Stroke in Type 2 Diabetic Patients Stroke, March 1, 2008; 39(3): 1036 - 1038. [Abstract] [Full Text] [PDF]
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M. Janghorbani, F. B. Hu, W. C. Willett, T. Y. Li, J. E. Manson, G. Logroscino, and K. M. Rexrode Prospective Study of Type 1 and Type 2 Diabetes and Risk of Stroke Subtypes: The Nurses' Health Study Diabetes Care, July 1, 2007; 30(7): 1730 - 1735. [Abstract] [Full Text] [PDF]
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 Authors/Task Force Members, L. Ryden, E. Standl, M. Bartnik, G. V. d. Berghe, J. Betteridge, M.-J. de Boer, F. Cosentino, B. Jonsson, M. Laakso, et al. Guidelines on diabetes, pre-diabetes, and cardiovascular diseases: full text: The Task Force on Diabetes and Cardiovascular Diseases of the European Society of Cardiology (ESC) and of the European Association for the Study of Diabetes (EASD) Eur. Heart J. Suppl., June 1, 2007; 9(suppl_C): C3 - C74. [Full Text] [PDF]
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C. B. Giorda, A. Avogaro, M. Maggini, F. Lombardo, E. Mannucci, S. Turco, S. S. Alegiani, R. Raschetti, M. Velussi, E. Ferrannini, et al. Incidence and Risk Factors for Stroke in Type 2 Diabetic Patients: The DAI Study Stroke, April 1, 2007; 38(4): 1154 - 1160. [Abstract] [Full Text] [PDF]
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R. Wilcox, M.-G. Bousser, D. J. Betteridge, G. Schernthaner, V. Pirags, S. Kupfer, J. Dormandy, and for the PROactive Investigators Effects of Pioglitazone in Patients With Type 2 Diabetes With or Without Previous Stroke: Results From PROactive (PROspective pioglitAzone Clinical Trial In macroVascular Events 04) Stroke, March 1, 2007; 38(3): 865 - 873. [Abstract] [Full Text] [PDF]
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 Authors/Task Force Members, L. Ryden, E. Standl, M. Bartnik, G. Van den Berghe, J. Betteridge, M.-J. de Boer, F. Cosentino, B. Jonsson, M. Laakso, et al. Guidelines on diabetes, pre-diabetes, and cardiovascular diseases: executive summary: The Task Force on Diabetes and Cardiovascular Diseases of the European Society of Cardiology (ESC) and of the European Association for the Study of Diabetes (EASD) Eur. Heart J., January 1, 2007; 28(1): 88 - 136. [Full Text] [PDF]
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G. Hu, C. Sarti, P. Jousilahti, M. Peltonen, Q. Qiao, R. Antikainen, and J. Tuomilehto The Impact of History of Hypertension and Type 2 Diabetes at Baseline on the Incidence of Stroke and Stroke Mortality Stroke, December 1, 2005; 36(12): 2538 - 2543. [Abstract] [Full Text] [PDF]
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 N. D Luscombe-Marsh, M. Noakes, G. A Wittert, J. B Keogh, P. Foster, and P. M Clifton Carbohydrate-restricted diets high in either monounsaturated fat or protein are equally effective at promoting fat loss and improving blood lipids Am. J. Clinical Nutrition, April 1, 2005; 81(4): 762 - 772. [Abstract] [Full Text] [PDF]
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 E. Selvin, S. Marinopoulos, G. Berkenblit, T. Rami, F. L. Brancati, N. R. Powe, and S. H. Golden Meta-Analysis: Glycosylated Hemoglobin and Cardiovascular Disease in Diabetes Mellitus Ann Intern Med, September 21, 2004; 141(6): 421 - 431. [Abstract] [Full Text] [PDF]
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C. R.L. Cardoso, G. F. Salles, and W. Deccache QTc Interval Prolongation Is a Predictor of Future Strokes in Patients With Type 2 Diabetes Mellitus Stroke, September 1, 2003; 34(9): 2187 - 2194. [Abstract] [Full Text] [PDF]
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S. Vijan and R. A. Hayward Treatment of Hypertension in Type 2 Diabetes Mellitus: Blood Pressure Goals, Choice of Agents, and Setting Priorities in Diabetes Care Ann Intern Med, April 1, 2003; 138(7): 593 - 602. [Abstract] [Full Text] [PDF]
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S.-E. Megherbi, C. Milan, D. Minier, G. Couvreur, G.-V. Osseby, K. Tilling, A. Di Carlo, D. Inzitari, C. D.A. Wolfe, T. Moreau, et al. Association Between Diabetes and Stroke Subtype on Survival and Functional Outcome 3 Months After Stroke: Data From the European BIOMED Stroke Project Stroke, March 1, 2003; 34(3): 688 - 694. [Abstract] [Full Text] [PDF]
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S. P. Laing, A. J. Swerdlow, L. M. Carpenter, S. D. Slater, A. C. Burden, J. L. Botha, A. D. Morris, N. R. Waugh, W. Gatling, E. A.M. Gale, et al. Mortality From Cerebrovascular Disease in a Cohort of 23 000 Patients With Insulin-Treated Diabetes Stroke, February 1, 2003; 34(2): 418 - 421. [Abstract] [Full Text] [PDF]
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 J. R. Sowers and S. Haffner Treatment of Cardiovascular and Renal Risk Factors in the Diabetic Hypertensive Hypertension, December 1, 2002; 40(6): 781 - 788. [Full Text] [PDF]
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 A. H. FRIEDLANDER, N. R. GARRETT, and D. C. NORMAN The prevalence of calcified carotid artery atheromas on the panoramic radiographs of patients with type 2 diabetes mellitus J Am Dent Assoc, November 1, 2002; 133(11): 1516 - 1523. [Abstract] [Full Text] [PDF]
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V. Kothari, R. J. Stevens, A. I. Adler, I. M. Stratton, S. E. Manley, H. A. Neil, and R. R. Holman UKPDS 60: Risk of Stroke in Type 2 Diabetes Estimated by the UK Prospective Diabetes Study Risk Engine Stroke, July 1, 2002; 33(7): 1776 - 1781. [Abstract] [Full Text] [PDF]
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 U. Krishnamurti and M. W. Steffes Glycohemoglobin: A Primary Predictor of the Development or Reversal of Complications of Diabetes Mellitus Clin. Chem., July 1, 2001; 47(7): 1157 - 1165. [Abstract] [Full Text] [PDF]
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 I. M Stratton, A. I Adler, H A. W Neil, D. R Matthews, S. E Manley, C. A Cull, D. Hadden, R. C Turner, and R. R Holman Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study BMJ, August 12, 2000; 321(7258): 405 - 412. [Abstract] [Full Text]
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A. I Adler, I. M Stratton, H A. W Neil, J. S Yudkin, D. R Matthews, C. A Cull, A. D Wright, R. C Turner, and R. R Holman Association of systolic blood pressure with macrovascular and microvascular complications of type 2 diabetes (UKPDS 36): prospective observational study BMJ, August 12, 2000; 321(7258): 412 - 419. [Abstract] [Full Text]
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F. Guerrero-Romero and M. Rodriguez-Moran Proteinuria Is an Independent Risk Factor for Ischemic Stroke in Non–Insulin-Dependent Diabetes Mellitus Stroke, September 1, 1999; 30(9): 1787 - 1791. [Abstract] [Full Text] [PDF]
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S. Lehto, L. Niskanen, T. Ronnemaa, and M. Laakso Serum Uric Acid Is a Strong Predictor of Stroke in Patients With Non–Insulin-Dependent Diabetes Mellitus Stroke, March 1, 1998; 29(3): 635 - 639. [Abstract] [Full Text] [PDF]
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H. Miettinen, S. M. Haffner, S. Lehto, T. Ronnemaa, K. Pyorala, and M. Laakso Proteinuria Predicts Stroke and Other Atherosclerotic Vascular Disease Events in Nondiabetic and Non–Insulin-Dependent Diabetic Subjects Stroke, November 1, 1996; 27(11): 2033 - 2039. [Abstract] [Full Text]
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 E. M. Brooks-Asplund, A. A. Shoukas, S.-Y. Kim, S. A. Burke, and D. E. Berkowitz Estrogen has opposing effects on vascular reactivity in obese, insulin-resistant male Zucker rats J Appl Physiol, May 1, 2002; 92(5): 2035 - 2044. [Abstract] [Full Text] [PDF]
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