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Type 2 diabetes but not coronary atherosclerosis is an independent determinant of impaired mobility in angiographied coronary patients
diabetes research and clinical practice 82 (2008) 185–189
available at www.sciencedirect.com
journal homepage: www.elsevier.com/locate/diabres
Type 2 diabetes but not coronary atherosclerosis is an independent determinant of impaired mobility in angiographied coronary patients Christoph H. Saely a,b,c,1, Thomas Dyballa a,c,1, Alexander Vonbank a,c, Magdalena Woess a, Philipp Rein a,b,c, Stefan Beer a,b,c, Vlado Jankovic a, Christian Boehnel a, Stefan Aczel a,b, Heinz Drexel a,b,c,d,* a
Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Feldkirch, Austria Department of Medicine, Academic Teaching Hospital Feldkirch, Carinagasse 47, A-6807 Feldkirch, Austria c Private University in the Principality of Liechtenstein, Triesen, Liechtenstein d Drexel University College of Medicine, Philadelphia, PA, USA b
article info
abstract
Article history:
Aims: We aimed at determining the associations of type 2 diabetes (T2DM) and of angio-
Received 31 March 2008
graphically determined coronary artery disease (CAD) with impaired mobility.
Received in revised form
Methods: We enrolled 747 consecutive patients undergoing coronary angiography for the
15 July 2008
evaluation of stable CAD. Mobility was assessed by the standardized timed-up-and-go (TUG)
Accepted 12 August 2008
test, a functional test of physical performance.
Published on line 1 October 2008
Results: Mobility was impaired (TUG time >10 s) in 199 (26.6%) patients. The proportion of subjects with impaired mobility was higher among patients with T2DM than among non-
Keywords:
diabetic individuals (40.2% vs. 22.0%; p < 0.001), whereas it did not differ significantly
Mobility
between patients with significant coronary stenoses 50% and those without such lesions
Timed-up-and-go test
( p = 0.802). Multivariate adjustment in logistic regression analyses confirmed that T2DM
Type 2 diabetes
(adjusted odds ratio (OR) = 2.05 [95% CI 1.35–3.11]; p = 0.001) but not the presence of sig-
Coronary artery disease
nificant coronary stenoses (adjusted OR = 0.81 [0.55–1.21]; p = 0.306) was independently
Coronary angiography
associated with impaired mobility. Conclusions: T2DM but not coronary atherosclerosis is an independent determinant of impaired mobility in the high risk population of angiographied coronary patients. Mobility enhancing exercise programs are needed for diabetic coronary patients. # 2008 Elsevier Ireland Ltd. All rights reserved.
1.
Introduction
Because coronary artery disease (CAD) is the major cause of death in type 2 diabetes (T2DM) [1], the prevention of cardiovascular events in these patients is of paramount importance. Physical exercise induces numerous beneficial
metabolic effects [2,3] and has a considerable potential for cardiovascular risk reduction [4,5]. In particular, it improves insulin resistance, the very central disorder of T2DM [6,7]. Exercise therefore is a cornerstone in the management of patients with T2DM [8] as well as of patients with CAD [9].
* Corresponding author at: Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Carinagasse 47, Feldkirch, Austria. Tel.: +43 5522 303 2670; fax: +43 5522 303 7533. E-mail address: [email protected] (H. Drexel). 1 Both authors contributed equally to this work. 0168-8227/$ – see front matter # 2008 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.diabres.2008.08.007
186
diabetes research and clinical practice 82 (2008) 185–189
Already moderately impaired mobility may pose a serious obstacle to adequate physical activity. It is therefore important to identify risk factors for impaired mobility, in order to facilitate timely screening of at-risk patients and to specifically enhance or at least preserve their mobility and physical activity. Coronary angiography in current clinical practice is the gold standard for the evaluation of CAD in high risk individuals [10]. Cardiovascular risk is high in patients undergoing coronary angiography, in particular among individuals with T2DM [11,12]. No data on the risk factors for impaired mobility are available for this important patient population. We therefore aimed at investigating the prevalence and the determinants of impaired mobility in a large consecutive series of angiographied coronary patients, including both patients with T2DM and non-diabetic subjects. We hypothesized that both the presence of T2DM and angiographically determined coronary atherosclerosis would increase the risk of impaired mobility.
2.
Subjects, materials and methods
2.1.
Study subjects
From August 2005 to December 2007 we performed standardized timed-up-and-go (TUG) tests in 751 consecutive Caucasian patients who were referred to coronary angiography for the evaluation of established or suspected stable CAD. Referral to coronary angiography thus was the inclusion criterion. Exclusion criteria were unstable CAD (patients who had suffered myocardial infarctions or acute coronary syndromes within three months prior to the baseline angiography therefore were not enrolled) and major amputations above the ankle. Further, four patients with type 1 diabetes (Cpeptide negative) were excluded from the analyses. Data thus are reported for 747 patients. Information on conventional cardiovascular risk factors was obtained by a standardized interview; and systolic/ diastolic blood pressure was measured by the Riva-Rocci method under resting conditions in a sitting position at the day of hospital entry at least 5 h after hospitalization. Hypertension was defined according to the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure [13], and T2DM was diagnosed according to World Health Organization criteria [14]. All patients who did not have previously diagnosed diabetes underwent oral glucose tolerance tests. Height and weight were recorded, and body mass index (BMI) was calculated as body weight (kg)/height (m)2. Overall, 71% of our patients were on aspirin, 50.3% on statins, 1.5% on fibrates, 12.3% on calcium antagonists, 55.8% on beta adrenoreceptor blocking agents, 36.5% on angiotensin converting enzyme inhibitors, and 18.3% on angiotensin II receptor blocking agents. Among patients with T2DM, 20.3%, 24.6%, 41.7%, 0.5%, and 3.2% were receiving – alone or in combination – insulin, sulfonylurea, metformin, acarbose, and glitazones, respectively. To measure mobility, a standardized TUG test was performed. In this functional test of physical performance, patients are asked to rise from a chair with armrests, walk over
a distance of 3 m, go back to the chair, and sit down again. The required time (TUG time) was measured with a stopwatch. According to Podsiadlo and Richardson [15] a TUG time >10 s was considered to indicate impaired mobility. Coronary angiography was performed with the Judkins technique. Coronary artery stenoses with lumen narrowing of 50% or more were considered significant, and coronary arteries were defined as normal in the absence of any visible lumen narrowing at angiography, as described previously [16,17]. Venous blood samples were collected after an overnight fast of 12 h before angiography was performed, and laboratory measurements were performed as described previously [18]. The Ethics Committee of the University of Innsbruck approved the present study, and all participants gave written informed consent.
2.2.
Statistical analysis
Differences in patient characteristics were tested for statistical significance with the Chi square test for categorical variables; the Mann–Whitney U-test was used for continuous variables. Independent associations with the presence of coronary atherosclerosis and with T2DM were evaluated with multivariate logistic regression analysis. For these analyses, continuous variables were z-transformed. To test for independent determinants of continuous variables, analysis of covariance (ANCOVA) was performed, using a general linear model approach. Results are given as mean standard deviation if not denoted otherwise. Sample size calculations showed that with a standard deviation of 30% of the population mean, 104 subjects would be sufficient per group to achieve a >95% power to detect a difference of 15% between study groups at a two-tailed alpha fault of 0.05. Statistical analyses were performed with the software package SPSS 11.0 for Windows (SPSS, Inc., Chicago, IL).
3.
Results
3.1.
Patient characteristics
Patient characteristics of our cohort were characteristic for a cohort of angiographied coronary patients, with a mean age of 65 10 years, a preponderance of male gender (64.1%), and a high prevalence of hypertension (71.2%), smoking (60.1%) and T2DM (25.3%). Table 1 summarizes the patient characteristics with respect to the presence of T2DM. Among patients with T2DM (n = 189), diabetes had been previously established in 72% (n = 136) and was newly diagnosed on the basis of fasting or postchallenge glucose in 28% (n = 53); the mean diabetes duration was 5.4 7.0 years.
3.2.
Results of the TUG tests
On average, our patients needed 9.6 3.1 s to complete the TUG test. TUG time was 10 s in 548 (73.4%), 11–20 s in 190 (25.4%), and >20 s in 9 (1.2%) of the investigated patients. Thus, impaired mobility was diagnosed in 199 (26.6%) subjects. The proportion of subjects with impaired mobility was significantly higher among patients with T2DM than among
diabetes research and clinical practice 82 (2008) 185–189
187
Table 1 – Characteristics of the study population No diabetes (n = 558) Age (years) Male gender (%; n) Body mass index (kg/m2) Significant coronary stenoses 50% (%; n) Hypertension (%; n) Smoking (%; n) Systolic blood pressure (mmHg) Diastolic blood pressure (mmHg) Fasting plasma glucose (mg/dl) HbA1c (%) Triglycerides (mg/dl) Total cholesterol (mg/dl) HDL cholesterol (mg/dl)
65 11 63.6 (n = 355) 27.2 4.0 51.3 (n = 286) 67.2 (n = 375) 57.9 (n = 323) 135 17 82 9 97 10 5.7 0.3 133 90 200 47 59 17
T2DM (n = 189) 66 9 65.6 (n = 124) 29.8 4.1 66.1 (n = 125) 83.1 (n = 157) 66.7 (n = 126) 138 16 82 10 154 52 7.4 1.5 162 97 181 42 51 13
p-Value 0.139 0.622 <0.001 <0.001 <0.001 0.033 0.013 0.726 <0.001 <0.001 <0.001 <0.001 <0.001
T2DM denotes type 2 diabetes. To convert values for triglycerides to mmol/l multiply by 0.0113, and to convert values for total cholesterol, or HDL cholesterol to mmol/l multiply by 0.0259.
non-diabetic individuals (40.2% vs. 22.0%; p < 0.001; Fig. 1A), whereas it did not differ significantly between patients with significant coronary stenoses and those without such lesions (27.0 vs. 26.2%; p = 0.802; Fig. 1B).
3.3. CAD
Subgroup analyses with respect to both diabetes and
of impaired mobility differed significantly between patients with significant coronary stenoses and those without such lesions. The prevalence of impaired mobility was significantly higher among patients who had T2DM but not significant CAD than among those who had significant CAD but not T2DM ( p = 0.007).
3.4. From the patients with T2DM, significant coronary stenoses were present in 125 (66.1%) and 64 (33.9%) did not have significant coronary stenoses. Among non-diabetic subjects, 286 (51.3%) had significant coronary stenoses and 272 (48.7%) did not have such lesions. Patient characteristics in the subgroups with respect to both T2DM and CAD are summarized in Table 2. The prevalence of impaired mobility was higher in T2DM patients than in non-diabetic subjects both among patients who had significant coronary stenoses (42.6% vs. 20.3%; p < 0.001) and in subjects who did not have such lesions (35.9% vs. 23.9%; p = 0.049). However, neither among T2DM patients (42.4% vs. 35.9%; p = 0.392) nor among nondiabetic individuals (20.3% vs. 23.9%; p = 0.303) the prevalence
Fig. 1 – Associations of type 2 diabetes and of coronary atherosclerosis with impaired mobility. (A) Association between type 2 diabetes and impaired mobility. Impaired mobility is defined as a timed-up-and-go test time >10 s; T2DM denotes type 2 diabetes; ‘*’ denotes statistical significance. (B) Association between the presence of significant coronary stenoses and impaired mobility. Impaired mobility is defined as a timed-up-and-go test time >10 s; Sign. stenoses denotes significant coronary stenoses.
Multivariate analyses
Adjustment for age, gender, BMI, smoking, and hypertension in logistic regression analyses confirmed that T2DM (adjusted OR = 2.05 [95% CI 1.35–3.11]; p = 0.001) but not the presence of significant coronary stenoses (adjusted OR = 0.81 [0.55–1.21]; p = 0.306) was independently associated with impaired mobility. In the same model, further independent determinants of impaired mobility were age (standardized adjusted OR = 3.27 [2.54–4.21]; p < 0.001), female gender (adjusted OR 1.76 [1.16– 2.69]; p = 0.008), and body mass index (standardized adjusted OR = 1.49 [1.23–1.81]; p < 0.001). The prevalence rates of impaired mobility were 22.9%, 24.3%, and 33.6% in subjects with a BMI < 25 kg/m2, in overweight subjects (BMI 25–29.9 kg/ m2), and in obese patients (BMI 30 kg/m2), respectively ( ptrend = 0.013). Among patients with T2DM, after adjustment for gender, BMI, hypertension, smoking, and the presence of significant coronary stenoses, both age (standardized adjusted OR = 2.93 [1.87–4.58]; p < 0.001) and diabetes duration (standardized adjusted OR = 1.60 [1.12–2.27]; p < 0.009) significantly predicted impaired mobility. Also when the TUG time was treated as a continuous variable, T2DM (F = 19.63; p < 0.001) besides age (F = 141.12; p < 0.001), female gender (F = 4.78; p = 0.029), and BMI (F = 42.04; p < 0.001), but not the presence of significant coronary stenoses (F = 0.538; p = 0.463) in ANCOVA proved significantly and independently associated with impaired mobility.
4.
Discussion
This is the first investigation addressing the determinants of impaired mobility among angiographied coronary patients. Our data show that T2DM, but not coronary atherosclerosis is
188
diabetes research and clinical practice 82 (2008) 185–189
Table 2 – Patient characteristics with respect to both coronary artery disease and diabetes No significant coronary stenoses
Age (years) Male gender (%; n) Body mass index (kg/m2) Hypertension (%; n) Smoking (%; n) Systolic blood pressure (mmHg) Diastolic blood pressure (mmHg) Fasting plasma glucose (mg/dl) HbA1c (%) Triglycerides (mg/dl) Total cholesterol (mg/dl) HDL cholesterol (mg/dl)
Significant coronary stenoses
No diabetes (n = 272)
T2DM (n = 64)
p-Value
No diabetes (n = 286)
T2DM (n = 125)
63 10 51.5 (n = 140) 27.5 4.4 62.5 (n = 170) 52.6 (n = 143) 134 16 82 9 96 10 5.7 0.3 131 87 204 47 61 19
65 10 56.3 (n = 36) 30.9 5.6 81.3 (n = 52) 59.4 (n = 38) 137 17 83 10 159 61 7.4 1.7 170 102 190 45 51 12
0.228 0.492 <0.001 0.004 0.327 0.100 0.427 <0.001 <0.001 <0.001 0.025 <0.001
66 11 75.2 (n = 215) 27.0 3.6 71.7 (n = 205) 62.9 (n = 180) 136 19 82 9 97 10 5.7 0.3 135 92 198 47 57 15
67 9 70.4 (n = 88) 29.2 4.7 84.0 (n = 105) 70.4 (n = 88) 138 16 82 10 151 46 7.3 1.3 158 93 176 40 51 14
p-Value 0.742 0.312 <0.001 0.007 0.144 0.060 0.960 <0.001 <0.001 0.004 <0.001 0.001
T2DM denotes type 2 diabetes. To convert values for triglycerides to mmol/l multiply by 0.0113, and to convert values for total cholesterol, or HDL cholesterol to mmol/l multiply by 0.0259.
independently associated with impaired mobility in this clinically important patient population. Among our patients with T2DM, diabetes duration was strongly and independently associated with impaired mobility. This important result points to a causal relationship between T2DM and impaired mobility. Indeed, with increasing diabetes duration, the prevalence of diabetes-related disorders such as diabetic retinopathy [19] or diabetic neuropathy [20] increases. The presence of diabetes complications in turn has been shown to be associated with decreased lower body mobility in diabetic patients [21], which has a major impact on the performance in the TUG test. Besides T2DM, age, female gender and BMI were significantly associated with impaired mobility in our investigation. Our results from angiographied coronary patients are well in line with reports on associations of diabetes [22], increasing age [23], female gender [23,24], or high BMI [23,25] with reduced mobility in other populations. T2DM is strongly associated with obesity. Our investigation reveals the important fact that T2DM and BMI are mutually independent risk determinants of impaired mobility. Through the angiographical characterization of our study participants we could further demonstrate that T2DM is associated with impaired mobility independent from the coronary artery state. CAD is the major macrovascular complication in T2DM [1]. No previous data on a potential impact of angiographically characterized CAD on mobility are available from the literature. Even though adequately powered, our investigation did not show any association between TUG time and the presence of significant coronary stenoses at angiography. Thus, because CAD does not explain the impaired mobility of T2DM patients, diabetes complications other than CAD should account for the association of T2DM with impaired mobility. Indeed, associations of impaired mobility with peripheral arterial disease as well as with microvascular complications such as peripheral neuropathy or retinopathy have been shown in patients with diabetes [26]. In this context our finding that the major macrovascular complication of diabetes, coronary artery disease, is not associated with impaired mobility appears important.
Important strengths of our study are the angiographical characterization of the study subjects, the large sample size, and the detailed characterization of study subjects. By design, we focused on a selected patient population; our results therefore are not necessarily applicable to other populations. Because the determinants of mobility may differ between different patient populations, future studies on the determinants of mobility in other populations (especially in T2DM patients) would be of great interest. Our investigation addressed the associations of T2DM and of stable CAD with impaired mobility. Whereas our results show that stable CAD is not associated with decreased mobility, our data do not exclude that mobility may be impaired after an acute coronary event. In conclusion, we have for the first time addressed the determinants of impaired mobility among angiographied coronary patients. Our data show that T2DM, but not coronary atherosclerosis is independently associated with impaired mobility in this important patient population. Even though impaired mobility is not associated with coronary atherosclerosis, screening for impaired mobility is valuable in coronary patients. Indeed, mobility was decreased in almost half of our coronary patients with T2DM and may pose a serious obstacle to physical exercise in these patients. Physical exercise, however, is crucially important in managing the high cardiovascular risk of patients with established coronary artery disease. Screening for impaired mobility and mobility enhancing exercise programs therefore appear necessary in diabetic coronary patients.
Acknowledgements The VIVIT institute thanks Dr. Egmond Frommelt and the Innovationsstiftung of the Liechtenstein Global Trust (LGT) Bank (Bendern, Liechtenstein), Dr. Karl Josef Hier and the Peter Goop Stiftung (Vaduz, Liechtenstein), the Fachhochschule Dornbirn (Dornbirn, Austria), and the Institute for Clinical Chemistry at the Academic Teaching Hospital Feldkirch (Feldkirch, Austria) for providing us with generous research grants. We are grateful to Franz Rauch and the Vorarlberger
diabetes research and clinical practice 82 (2008) 185–189
Industriellenvereinigung (Bregenz, Austria, to Dr. Peter Woess and the Vorarlberger Aerztekammer (Dornbirn, Austria), to Mag. Gabriela Du¨r and the Vorarlberger Landesregierung (Bregenz, Austria), to Dr. Elmar Bechter and the Vorarlberger Landessanita¨tsrat (Bregenz, Austria) and to Luis Patsch, Director, Vorarlberger Landeskrankenhaus-Betriebsgesellschaft (Feldkirch, Austria), for continuously supporting our Research Institute. Conflict of interest The authors declare that they have no conflict of interest.
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available at www.sciencedirect.com
journal homepage: www.elsevier.com/locate/diabres
Type 2 diabetes but not coronary atherosclerosis is an independent determinant of impaired mobility in angiographied coronary patients Christoph H. Saely a,b,c,1, Thomas Dyballa a,c,1, Alexander Vonbank a,c, Magdalena Woess a, Philipp Rein a,b,c, Stefan Beer a,b,c, Vlado Jankovic a, Christian Boehnel a, Stefan Aczel a,b, Heinz Drexel a,b,c,d,* a
Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Feldkirch, Austria Department of Medicine, Academic Teaching Hospital Feldkirch, Carinagasse 47, A-6807 Feldkirch, Austria c Private University in the Principality of Liechtenstein, Triesen, Liechtenstein d Drexel University College of Medicine, Philadelphia, PA, USA b
article info
abstract
Article history:
Aims: We aimed at determining the associations of type 2 diabetes (T2DM) and of angio-
Received 31 March 2008
graphically determined coronary artery disease (CAD) with impaired mobility.
Received in revised form
Methods: We enrolled 747 consecutive patients undergoing coronary angiography for the
15 July 2008
evaluation of stable CAD. Mobility was assessed by the standardized timed-up-and-go (TUG)
Accepted 12 August 2008
test, a functional test of physical performance.
Published on line 1 October 2008
Results: Mobility was impaired (TUG time >10 s) in 199 (26.6%) patients. The proportion of subjects with impaired mobility was higher among patients with T2DM than among non-
Keywords:
diabetic individuals (40.2% vs. 22.0%; p < 0.001), whereas it did not differ significantly
Mobility
between patients with significant coronary stenoses 50% and those without such lesions
Timed-up-and-go test
( p = 0.802). Multivariate adjustment in logistic regression analyses confirmed that T2DM
Type 2 diabetes
(adjusted odds ratio (OR) = 2.05 [95% CI 1.35–3.11]; p = 0.001) but not the presence of sig-
Coronary artery disease
nificant coronary stenoses (adjusted OR = 0.81 [0.55–1.21]; p = 0.306) was independently
Coronary angiography
associated with impaired mobility. Conclusions: T2DM but not coronary atherosclerosis is an independent determinant of impaired mobility in the high risk population of angiographied coronary patients. Mobility enhancing exercise programs are needed for diabetic coronary patients. # 2008 Elsevier Ireland Ltd. All rights reserved.
1.
Introduction
Because coronary artery disease (CAD) is the major cause of death in type 2 diabetes (T2DM) [1], the prevention of cardiovascular events in these patients is of paramount importance. Physical exercise induces numerous beneficial
metabolic effects [2,3] and has a considerable potential for cardiovascular risk reduction [4,5]. In particular, it improves insulin resistance, the very central disorder of T2DM [6,7]. Exercise therefore is a cornerstone in the management of patients with T2DM [8] as well as of patients with CAD [9].
* Corresponding author at: Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Carinagasse 47, Feldkirch, Austria. Tel.: +43 5522 303 2670; fax: +43 5522 303 7533. E-mail address: [email protected] (H. Drexel). 1 Both authors contributed equally to this work. 0168-8227/$ – see front matter # 2008 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.diabres.2008.08.007
186
diabetes research and clinical practice 82 (2008) 185–189
Already moderately impaired mobility may pose a serious obstacle to adequate physical activity. It is therefore important to identify risk factors for impaired mobility, in order to facilitate timely screening of at-risk patients and to specifically enhance or at least preserve their mobility and physical activity. Coronary angiography in current clinical practice is the gold standard for the evaluation of CAD in high risk individuals [10]. Cardiovascular risk is high in patients undergoing coronary angiography, in particular among individuals with T2DM [11,12]. No data on the risk factors for impaired mobility are available for this important patient population. We therefore aimed at investigating the prevalence and the determinants of impaired mobility in a large consecutive series of angiographied coronary patients, including both patients with T2DM and non-diabetic subjects. We hypothesized that both the presence of T2DM and angiographically determined coronary atherosclerosis would increase the risk of impaired mobility.
2.
Subjects, materials and methods
2.1.
Study subjects
From August 2005 to December 2007 we performed standardized timed-up-and-go (TUG) tests in 751 consecutive Caucasian patients who were referred to coronary angiography for the evaluation of established or suspected stable CAD. Referral to coronary angiography thus was the inclusion criterion. Exclusion criteria were unstable CAD (patients who had suffered myocardial infarctions or acute coronary syndromes within three months prior to the baseline angiography therefore were not enrolled) and major amputations above the ankle. Further, four patients with type 1 diabetes (Cpeptide negative) were excluded from the analyses. Data thus are reported for 747 patients. Information on conventional cardiovascular risk factors was obtained by a standardized interview; and systolic/ diastolic blood pressure was measured by the Riva-Rocci method under resting conditions in a sitting position at the day of hospital entry at least 5 h after hospitalization. Hypertension was defined according to the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure [13], and T2DM was diagnosed according to World Health Organization criteria [14]. All patients who did not have previously diagnosed diabetes underwent oral glucose tolerance tests. Height and weight were recorded, and body mass index (BMI) was calculated as body weight (kg)/height (m)2. Overall, 71% of our patients were on aspirin, 50.3% on statins, 1.5% on fibrates, 12.3% on calcium antagonists, 55.8% on beta adrenoreceptor blocking agents, 36.5% on angiotensin converting enzyme inhibitors, and 18.3% on angiotensin II receptor blocking agents. Among patients with T2DM, 20.3%, 24.6%, 41.7%, 0.5%, and 3.2% were receiving – alone or in combination – insulin, sulfonylurea, metformin, acarbose, and glitazones, respectively. To measure mobility, a standardized TUG test was performed. In this functional test of physical performance, patients are asked to rise from a chair with armrests, walk over
a distance of 3 m, go back to the chair, and sit down again. The required time (TUG time) was measured with a stopwatch. According to Podsiadlo and Richardson [15] a TUG time >10 s was considered to indicate impaired mobility. Coronary angiography was performed with the Judkins technique. Coronary artery stenoses with lumen narrowing of 50% or more were considered significant, and coronary arteries were defined as normal in the absence of any visible lumen narrowing at angiography, as described previously [16,17]. Venous blood samples were collected after an overnight fast of 12 h before angiography was performed, and laboratory measurements were performed as described previously [18]. The Ethics Committee of the University of Innsbruck approved the present study, and all participants gave written informed consent.
2.2.
Statistical analysis
Differences in patient characteristics were tested for statistical significance with the Chi square test for categorical variables; the Mann–Whitney U-test was used for continuous variables. Independent associations with the presence of coronary atherosclerosis and with T2DM were evaluated with multivariate logistic regression analysis. For these analyses, continuous variables were z-transformed. To test for independent determinants of continuous variables, analysis of covariance (ANCOVA) was performed, using a general linear model approach. Results are given as mean standard deviation if not denoted otherwise. Sample size calculations showed that with a standard deviation of 30% of the population mean, 104 subjects would be sufficient per group to achieve a >95% power to detect a difference of 15% between study groups at a two-tailed alpha fault of 0.05. Statistical analyses were performed with the software package SPSS 11.0 for Windows (SPSS, Inc., Chicago, IL).
3.
Results
3.1.
Patient characteristics
Patient characteristics of our cohort were characteristic for a cohort of angiographied coronary patients, with a mean age of 65 10 years, a preponderance of male gender (64.1%), and a high prevalence of hypertension (71.2%), smoking (60.1%) and T2DM (25.3%). Table 1 summarizes the patient characteristics with respect to the presence of T2DM. Among patients with T2DM (n = 189), diabetes had been previously established in 72% (n = 136) and was newly diagnosed on the basis of fasting or postchallenge glucose in 28% (n = 53); the mean diabetes duration was 5.4 7.0 years.
3.2.
Results of the TUG tests
On average, our patients needed 9.6 3.1 s to complete the TUG test. TUG time was 10 s in 548 (73.4%), 11–20 s in 190 (25.4%), and >20 s in 9 (1.2%) of the investigated patients. Thus, impaired mobility was diagnosed in 199 (26.6%) subjects. The proportion of subjects with impaired mobility was significantly higher among patients with T2DM than among
diabetes research and clinical practice 82 (2008) 185–189
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Table 1 – Characteristics of the study population No diabetes (n = 558) Age (years) Male gender (%; n) Body mass index (kg/m2) Significant coronary stenoses 50% (%; n) Hypertension (%; n) Smoking (%; n) Systolic blood pressure (mmHg) Diastolic blood pressure (mmHg) Fasting plasma glucose (mg/dl) HbA1c (%) Triglycerides (mg/dl) Total cholesterol (mg/dl) HDL cholesterol (mg/dl)
65 11 63.6 (n = 355) 27.2 4.0 51.3 (n = 286) 67.2 (n = 375) 57.9 (n = 323) 135 17 82 9 97 10 5.7 0.3 133 90 200 47 59 17
T2DM (n = 189) 66 9 65.6 (n = 124) 29.8 4.1 66.1 (n = 125) 83.1 (n = 157) 66.7 (n = 126) 138 16 82 10 154 52 7.4 1.5 162 97 181 42 51 13
p-Value 0.139 0.622 <0.001 <0.001 <0.001 0.033 0.013 0.726 <0.001 <0.001 <0.001 <0.001 <0.001
T2DM denotes type 2 diabetes. To convert values for triglycerides to mmol/l multiply by 0.0113, and to convert values for total cholesterol, or HDL cholesterol to mmol/l multiply by 0.0259.
non-diabetic individuals (40.2% vs. 22.0%; p < 0.001; Fig. 1A), whereas it did not differ significantly between patients with significant coronary stenoses and those without such lesions (27.0 vs. 26.2%; p = 0.802; Fig. 1B).
3.3. CAD
Subgroup analyses with respect to both diabetes and
of impaired mobility differed significantly between patients with significant coronary stenoses and those without such lesions. The prevalence of impaired mobility was significantly higher among patients who had T2DM but not significant CAD than among those who had significant CAD but not T2DM ( p = 0.007).
3.4. From the patients with T2DM, significant coronary stenoses were present in 125 (66.1%) and 64 (33.9%) did not have significant coronary stenoses. Among non-diabetic subjects, 286 (51.3%) had significant coronary stenoses and 272 (48.7%) did not have such lesions. Patient characteristics in the subgroups with respect to both T2DM and CAD are summarized in Table 2. The prevalence of impaired mobility was higher in T2DM patients than in non-diabetic subjects both among patients who had significant coronary stenoses (42.6% vs. 20.3%; p < 0.001) and in subjects who did not have such lesions (35.9% vs. 23.9%; p = 0.049). However, neither among T2DM patients (42.4% vs. 35.9%; p = 0.392) nor among nondiabetic individuals (20.3% vs. 23.9%; p = 0.303) the prevalence
Fig. 1 – Associations of type 2 diabetes and of coronary atherosclerosis with impaired mobility. (A) Association between type 2 diabetes and impaired mobility. Impaired mobility is defined as a timed-up-and-go test time >10 s; T2DM denotes type 2 diabetes; ‘*’ denotes statistical significance. (B) Association between the presence of significant coronary stenoses and impaired mobility. Impaired mobility is defined as a timed-up-and-go test time >10 s; Sign. stenoses denotes significant coronary stenoses.
Multivariate analyses
Adjustment for age, gender, BMI, smoking, and hypertension in logistic regression analyses confirmed that T2DM (adjusted OR = 2.05 [95% CI 1.35–3.11]; p = 0.001) but not the presence of significant coronary stenoses (adjusted OR = 0.81 [0.55–1.21]; p = 0.306) was independently associated with impaired mobility. In the same model, further independent determinants of impaired mobility were age (standardized adjusted OR = 3.27 [2.54–4.21]; p < 0.001), female gender (adjusted OR 1.76 [1.16– 2.69]; p = 0.008), and body mass index (standardized adjusted OR = 1.49 [1.23–1.81]; p < 0.001). The prevalence rates of impaired mobility were 22.9%, 24.3%, and 33.6% in subjects with a BMI < 25 kg/m2, in overweight subjects (BMI 25–29.9 kg/ m2), and in obese patients (BMI 30 kg/m2), respectively ( ptrend = 0.013). Among patients with T2DM, after adjustment for gender, BMI, hypertension, smoking, and the presence of significant coronary stenoses, both age (standardized adjusted OR = 2.93 [1.87–4.58]; p < 0.001) and diabetes duration (standardized adjusted OR = 1.60 [1.12–2.27]; p < 0.009) significantly predicted impaired mobility. Also when the TUG time was treated as a continuous variable, T2DM (F = 19.63; p < 0.001) besides age (F = 141.12; p < 0.001), female gender (F = 4.78; p = 0.029), and BMI (F = 42.04; p < 0.001), but not the presence of significant coronary stenoses (F = 0.538; p = 0.463) in ANCOVA proved significantly and independently associated with impaired mobility.
4.
Discussion
This is the first investigation addressing the determinants of impaired mobility among angiographied coronary patients. Our data show that T2DM, but not coronary atherosclerosis is
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Table 2 – Patient characteristics with respect to both coronary artery disease and diabetes No significant coronary stenoses
Age (years) Male gender (%; n) Body mass index (kg/m2) Hypertension (%; n) Smoking (%; n) Systolic blood pressure (mmHg) Diastolic blood pressure (mmHg) Fasting plasma glucose (mg/dl) HbA1c (%) Triglycerides (mg/dl) Total cholesterol (mg/dl) HDL cholesterol (mg/dl)
Significant coronary stenoses
No diabetes (n = 272)
T2DM (n = 64)
p-Value
No diabetes (n = 286)
T2DM (n = 125)
63 10 51.5 (n = 140) 27.5 4.4 62.5 (n = 170) 52.6 (n = 143) 134 16 82 9 96 10 5.7 0.3 131 87 204 47 61 19
65 10 56.3 (n = 36) 30.9 5.6 81.3 (n = 52) 59.4 (n = 38) 137 17 83 10 159 61 7.4 1.7 170 102 190 45 51 12
0.228 0.492 <0.001 0.004 0.327 0.100 0.427 <0.001 <0.001 <0.001 0.025 <0.001
66 11 75.2 (n = 215) 27.0 3.6 71.7 (n = 205) 62.9 (n = 180) 136 19 82 9 97 10 5.7 0.3 135 92 198 47 57 15
67 9 70.4 (n = 88) 29.2 4.7 84.0 (n = 105) 70.4 (n = 88) 138 16 82 10 151 46 7.3 1.3 158 93 176 40 51 14
p-Value 0.742 0.312 <0.001 0.007 0.144 0.060 0.960 <0.001 <0.001 0.004 <0.001 0.001
T2DM denotes type 2 diabetes. To convert values for triglycerides to mmol/l multiply by 0.0113, and to convert values for total cholesterol, or HDL cholesterol to mmol/l multiply by 0.0259.
independently associated with impaired mobility in this clinically important patient population. Among our patients with T2DM, diabetes duration was strongly and independently associated with impaired mobility. This important result points to a causal relationship between T2DM and impaired mobility. Indeed, with increasing diabetes duration, the prevalence of diabetes-related disorders such as diabetic retinopathy [19] or diabetic neuropathy [20] increases. The presence of diabetes complications in turn has been shown to be associated with decreased lower body mobility in diabetic patients [21], which has a major impact on the performance in the TUG test. Besides T2DM, age, female gender and BMI were significantly associated with impaired mobility in our investigation. Our results from angiographied coronary patients are well in line with reports on associations of diabetes [22], increasing age [23], female gender [23,24], or high BMI [23,25] with reduced mobility in other populations. T2DM is strongly associated with obesity. Our investigation reveals the important fact that T2DM and BMI are mutually independent risk determinants of impaired mobility. Through the angiographical characterization of our study participants we could further demonstrate that T2DM is associated with impaired mobility independent from the coronary artery state. CAD is the major macrovascular complication in T2DM [1]. No previous data on a potential impact of angiographically characterized CAD on mobility are available from the literature. Even though adequately powered, our investigation did not show any association between TUG time and the presence of significant coronary stenoses at angiography. Thus, because CAD does not explain the impaired mobility of T2DM patients, diabetes complications other than CAD should account for the association of T2DM with impaired mobility. Indeed, associations of impaired mobility with peripheral arterial disease as well as with microvascular complications such as peripheral neuropathy or retinopathy have been shown in patients with diabetes [26]. In this context our finding that the major macrovascular complication of diabetes, coronary artery disease, is not associated with impaired mobility appears important.
Important strengths of our study are the angiographical characterization of the study subjects, the large sample size, and the detailed characterization of study subjects. By design, we focused on a selected patient population; our results therefore are not necessarily applicable to other populations. Because the determinants of mobility may differ between different patient populations, future studies on the determinants of mobility in other populations (especially in T2DM patients) would be of great interest. Our investigation addressed the associations of T2DM and of stable CAD with impaired mobility. Whereas our results show that stable CAD is not associated with decreased mobility, our data do not exclude that mobility may be impaired after an acute coronary event. In conclusion, we have for the first time addressed the determinants of impaired mobility among angiographied coronary patients. Our data show that T2DM, but not coronary atherosclerosis is independently associated with impaired mobility in this important patient population. Even though impaired mobility is not associated with coronary atherosclerosis, screening for impaired mobility is valuable in coronary patients. Indeed, mobility was decreased in almost half of our coronary patients with T2DM and may pose a serious obstacle to physical exercise in these patients. Physical exercise, however, is crucially important in managing the high cardiovascular risk of patients with established coronary artery disease. Screening for impaired mobility and mobility enhancing exercise programs therefore appear necessary in diabetic coronary patients.
Acknowledgements The VIVIT institute thanks Dr. Egmond Frommelt and the Innovationsstiftung of the Liechtenstein Global Trust (LGT) Bank (Bendern, Liechtenstein), Dr. Karl Josef Hier and the Peter Goop Stiftung (Vaduz, Liechtenstein), the Fachhochschule Dornbirn (Dornbirn, Austria), and the Institute for Clinical Chemistry at the Academic Teaching Hospital Feldkirch (Feldkirch, Austria) for providing us with generous research grants. We are grateful to Franz Rauch and the Vorarlberger
diabetes research and clinical practice 82 (2008) 185–189
Industriellenvereinigung (Bregenz, Austria, to Dr. Peter Woess and the Vorarlberger Aerztekammer (Dornbirn, Austria), to Mag. Gabriela Du¨r and the Vorarlberger Landesregierung (Bregenz, Austria), to Dr. Elmar Bechter and the Vorarlberger Landessanita¨tsrat (Bregenz, Austria) and to Luis Patsch, Director, Vorarlberger Landeskrankenhaus-Betriebsgesellschaft (Feldkirch, Austria), for continuously supporting our Research Institute. Conflict of interest The authors declare that they have no conflict of interest.
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