Prevalence, incidence and progression of peripheral arterial disease in Asian Indian type 2 diabetic patients Jayasheel Eshcol, Saravanan Jebarani, Ranjit Mohan Anjana, Viswanathan Mohan, Rajendra Pradeepa PII: DOI: Reference:
S1056-8727(14)00128-7 doi: 10.1016/j.jdiacomp.2014.04.013 JDC 6264
To appear in:
Journal of Diabetes and Its Complications
Received date: Revised date: Accepted date:
10 September 2013 24 April 2014 24 April 2014
Please cite this article as: Eshcol, J., Jebarani, S., Anjana, R.M., Mohan, V. & Pradeepa, R., Prevalence, incidence and progression of peripheral arterial disease in Asian Indian type 2 diabetic patients, Journal of Diabetes and Its Complications (2014), doi: 10.1016/j.jdiacomp.2014.04.013
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Prevalence, incidence and progression of peripheral arterial disease in Asian Indian type 2 diabetic patients
T
Jayasheel Eshcol 1 Ranjit Mohan Anjana 2 Viswanathan Mohan 2
NU
SC
Rajendra Pradeepa 2
RI P
Saravanan Jebarani 2
University of Iowa Hospitals and Clinics, Iowa City, IA, USA
2
Madras Diabetes Research Foundation & Dr. Mohan’s Diabetes Specialities Centre, WHO Collaborating Centre for Non-communicable Diseases Prevention and Control & IDF Centre of Education, Chennai, India
MA
1
ED
Key words: Peripheral arterial disease, diabetes, prevalence, incidence, India, South Asians
PT
Running title: Incidence of peripheral arterial disease in type 2 diabetes
CE
Word count: 3206 Abstract: 208 No. of Tables: 2 No. of Figures: 1
AC
ADDRESS FOR CORRESPONDENCE Dr. V. MOHAN, M.D., FRCP (Lond, Edin, Glasg & Ire), Ph.D., D.Sc., FNASc., DIRECTOR & CHIEF OF DIABETES RESEARCH MADRAS DIABETES RESEARCH FOUNDATION & Dr. Mohan’s DIABETES SPECIALITIES CENTRE WHO Collaborating Centre for Noncommunicable Diseases Prevention & Control, 4, CONRAN SMITH ROAD, GOPALAPURAM, CHENNAI - 600 086, INDIA TEL NO: (9144) 4396 8888 FAX NO: (9144) 2835 0935 Email: [email protected] Website:www.drmohansdiabetes.com
ACCEPTED MANUSCRIPT ABSTRACT
Objective: To assess the prevalence, incidence, etiology and factors related to
RI P
T
progression of peripheral arterial disease [PAD] in Asian Indian type 2 diabetic patients.
Methods: Patients with type 2 diabetes (T2DM), with multiple doppler studies done
SC
between 2001-2011 at a tertiary diabetes center in south India, were included. Baseline clinical and biochemical characteristics and Ankle Brachial Index [ABI] measurements
NU
were abstracted from the electronic medical records.
MA
Results: 2512 T2DM patients were followed for an average of 7 years. 7.6% of the study population had PAD in 2001 [women-11.8%, men- 5.1%] with an adjusted odds ratio (OR) of 3.09 [Confidence Interval (CI):1.9- 4.9] for women. Prevalent PAD was
ED
associated with increased mortality [Hazards ratio (HR) 3.3, CI:1.4-7.7]. 280 new patients of PAD were identified- crude incidence, 17/1000 patient years with higher rates
PT
in females [HR 1.94, CI:1.4-2.7]. Age and duration of diabetes were the other predictors of incident PAD. Progression of PAD was seen in 16.5% of patients, with age (p=0.002)
CE
and HbA1c (p= 0.022) being the predictors.
AC
Conclusions: Women had a higher prevalence of PAD. Older age, female gender and duration of diabetes were related to an increased incidence of PAD. An elevated HbA1c being associated with progression of PAD stresses the need for strict control of diabetes.
ACCEPTED MANUSCRIPT INTRODUCTION
Peripheral arterial disease (PAD) is a disease in which, atherosclerotic (AS)
T
stenosis of arteries in organs other than the heart and the brain and most commonly,
RI P
arteries in the lower extremities are involved. Since AS is a generalized disease, PAD is associated with increased mortality due to coronary artery disease (Weitz et al., 1996).
SC
PAD can be diagnosed noninvasively by measuring the ankle brachial index [ABI]. Diabetes is a well known risk factor for PAD and the American Diabetes Association
NU
[ADA] recommends screening for PAD in all patients with diabetes >50 years of age and in diabetic patients younger than age 50 with at least one other risk factor for coronary
MA
artery disease (American Diabetes Association.,2004).
According to the recent national Indian Council of Medical Research - India
ED
Diabetes [ICMR-INDIAB] study currently, in India, there are 62.4 million people with type 2 diabetes mellitus [T2DM] (Anjana et al., 2011). Furthermore, the burden of micro and
PT
macrovascular complications is immense since T2DM occurs at a younger age compared to an occidental population of Europe (Pradeepa et al., 2010). Overall the
CE
prevalence of PAD is lower in Asian Indians, but this is mainly due to the younger age at onset of T2DM. As the population ages, the prevalence of PAD will dramatically
AC
increase. Moreover as India’s population is currently 1.2 billion this means that already there are ~4 million people with PAD assuming the prevalence of PAD to be 6.3% (Premalatha et al., 2000). Indeed it is now known that the economic burden of PAD is equivalent to that of CVD (Mahoney et al., 2010). It is therefore crucial to understand the risk factors for PAD in the Indian diabetic population. Several studies have published information on the prevalence of PAD in the diabetic population. However, only a few studies have reported data on incident PAD or progression of PAD, and there are none from India. Hence the present study was taken up, to assess the prevalence, incidence and progression of, and factors associated with, PAD in Asian Indian T2DM patients attending a large diabetic centre in south India.
ACCEPTED MANUSCRIPT METHODS
T
Study population
RI P
Patients with T2DM, with multiple doppler studies (2001-2011) at the Dr Mohan's Diabetes Specialties Centre, a tertiary diabetes care center in Chennai city in south
SC
India, were included in the study. The centre has state-of-the-art facilities for diabetes and its complications at fifteen clinics in different geographical areas in southern India.
NU
All the clinics are linked through electronic medical records, from which baseline clinical and biochemical characteristics and Ankle Brachial Index [ABI] measurements were
MA
abstracted.
A total of 7,586 T2DM patients aged 20 years and above were registered in
ED
2001, of whom 6893 patients had ABI measurements (response rate 90.9%). Of these, 2512 patients [36.4%] had at least one follow up ABI measurement between the years
PT
2001 and 2011. They were termed ‘responders’ and were included in the study. The rest, i.e., 4,381 of the 6,893 were considered as ‘non-responders’. The mean number of
CE
ABI measurements was 3.6 ± 1.8 during the follow up period and the mean time between first and last ABI was 7.0 ± 2.8 years. There were no significant differences in and the 4,381 non-responders
AC
the baseline values between the 2512 responders
[responders vs non-responders: age (years) 51 10 vs 52 12, p = 0.174; fasting plasma glucose (mg/dl): 160 58 vs 163 58, p = 0.074; duration of diabetes (years) 7.8 6.7 vs 8.0 6.7, p = 0.246; systolic blood pressure (mm Hg): 131 16 vs 132 17, p = 0.128; diastolic blood pressure (mm Hg): 82 7 vs 82 8, p = 0.584)]. The exclusion criteria included patients aged 1.30 was graded as unclassifiable. Progression of PAD was defined as a decrease in ABI>0.15 or a change in category of severity (Hirsch et al., 2006). For
AC
quantitative change the patients were grouped in 3 categories, less than −0.15, −0.15 to +0.15, and more than +0.15. The change in ABI was calculated using the first and last measurements of ABI.
Coronary artery disease [CAD] was diagnosed based on a past history of documented myocardial infarction and/or drug treatment for CAD (aspirin or nitrates) and/or electrocardiographic changes suggestive of ST segment depression and/or Qwave changes and/or T-wave changes using appropriate Minnesota codes (Rose et al., 1982).
Age was defined as the age at the time of the first examination i.e. in 2001.
ACCEPTED MANUSCRIPT Hypertension was diagnosed based on past medical history, drug treatment for hypertension, and/or if the patient had systolic blood pressure [SBP] of 140 mmHg or greater and/or diastolic blood pressure [DBP] of 90 mmHg (National High Blood
RI P
T
Pressure Education Program, 2003) .
Estimated Glomerular Filtration Rate [eGFR] was estimated using the Modification of
SC
Diet in Renal Disease [MDRD] study equation [mL/min/1.73 m2] (Levey et al.,1999 ). The formula used for calculating the GFR was: GFR = 186 × (serum creatinine)−1.154 ×
NU
Age−0.203 × (0.742 if female) × (1.210 if African-American [not applicable to our population])
MA
Smoking: Individuals were classified as ‘never smoked’ and ‘ever smoked’.
ED
Statistical Analysis
All statistical analyses were performed with SAS version 9.1 [SAS Institute, Cary, North
PT
Carolina]. Patients with initial or final ABI values greater than >1.3 were not analyzed for incidence or progression. Baseline characteristics of the population of patients with and
CE
without PAD were compared by logistic regression analysis. Cox proportional hazard models were used to determine the hazard ratio for mortality, incident PAD and
AC
progression. For incident PAD, time was measured from the initial ABI in 2001 to the date of ABI ≤0.9 for incident cases. For mortality, time was measured from the initial ABI to the date of death and date of last visit for censored cases. To build the Cox model, we first did a univariate analysis of each variable .Categorical variables were analyzed with Kaplan-Meir curves to ensure proportionality and the variable was included in the multivariate model if the log rank test had a p-value
S1056-8727(14)00128-7 doi: 10.1016/j.jdiacomp.2014.04.013 JDC 6264
To appear in:
Journal of Diabetes and Its Complications
Received date: Revised date: Accepted date:
10 September 2013 24 April 2014 24 April 2014
Please cite this article as: Eshcol, J., Jebarani, S., Anjana, R.M., Mohan, V. & Pradeepa, R., Prevalence, incidence and progression of peripheral arterial disease in Asian Indian type 2 diabetic patients, Journal of Diabetes and Its Complications (2014), doi: 10.1016/j.jdiacomp.2014.04.013
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Prevalence, incidence and progression of peripheral arterial disease in Asian Indian type 2 diabetic patients
T
Jayasheel Eshcol 1 Ranjit Mohan Anjana 2 Viswanathan Mohan 2
NU
SC
Rajendra Pradeepa 2
RI P
Saravanan Jebarani 2
University of Iowa Hospitals and Clinics, Iowa City, IA, USA
2
Madras Diabetes Research Foundation & Dr. Mohan’s Diabetes Specialities Centre, WHO Collaborating Centre for Non-communicable Diseases Prevention and Control & IDF Centre of Education, Chennai, India
MA
1
ED
Key words: Peripheral arterial disease, diabetes, prevalence, incidence, India, South Asians
PT
Running title: Incidence of peripheral arterial disease in type 2 diabetes
CE
Word count: 3206 Abstract: 208 No. of Tables: 2 No. of Figures: 1
AC
ADDRESS FOR CORRESPONDENCE Dr. V. MOHAN, M.D., FRCP (Lond, Edin, Glasg & Ire), Ph.D., D.Sc., FNASc., DIRECTOR & CHIEF OF DIABETES RESEARCH MADRAS DIABETES RESEARCH FOUNDATION & Dr. Mohan’s DIABETES SPECIALITIES CENTRE WHO Collaborating Centre for Noncommunicable Diseases Prevention & Control, 4, CONRAN SMITH ROAD, GOPALAPURAM, CHENNAI - 600 086, INDIA TEL NO: (9144) 4396 8888 FAX NO: (9144) 2835 0935 Email: [email protected] Website:www.drmohansdiabetes.com
ACCEPTED MANUSCRIPT ABSTRACT
Objective: To assess the prevalence, incidence, etiology and factors related to
RI P
T
progression of peripheral arterial disease [PAD] in Asian Indian type 2 diabetic patients.
Methods: Patients with type 2 diabetes (T2DM), with multiple doppler studies done
SC
between 2001-2011 at a tertiary diabetes center in south India, were included. Baseline clinical and biochemical characteristics and Ankle Brachial Index [ABI] measurements
NU
were abstracted from the electronic medical records.
MA
Results: 2512 T2DM patients were followed for an average of 7 years. 7.6% of the study population had PAD in 2001 [women-11.8%, men- 5.1%] with an adjusted odds ratio (OR) of 3.09 [Confidence Interval (CI):1.9- 4.9] for women. Prevalent PAD was
ED
associated with increased mortality [Hazards ratio (HR) 3.3, CI:1.4-7.7]. 280 new patients of PAD were identified- crude incidence, 17/1000 patient years with higher rates
PT
in females [HR 1.94, CI:1.4-2.7]. Age and duration of diabetes were the other predictors of incident PAD. Progression of PAD was seen in 16.5% of patients, with age (p=0.002)
CE
and HbA1c (p= 0.022) being the predictors.
AC
Conclusions: Women had a higher prevalence of PAD. Older age, female gender and duration of diabetes were related to an increased incidence of PAD. An elevated HbA1c being associated with progression of PAD stresses the need for strict control of diabetes.
ACCEPTED MANUSCRIPT INTRODUCTION
Peripheral arterial disease (PAD) is a disease in which, atherosclerotic (AS)
T
stenosis of arteries in organs other than the heart and the brain and most commonly,
RI P
arteries in the lower extremities are involved. Since AS is a generalized disease, PAD is associated with increased mortality due to coronary artery disease (Weitz et al., 1996).
SC
PAD can be diagnosed noninvasively by measuring the ankle brachial index [ABI]. Diabetes is a well known risk factor for PAD and the American Diabetes Association
NU
[ADA] recommends screening for PAD in all patients with diabetes >50 years of age and in diabetic patients younger than age 50 with at least one other risk factor for coronary
MA
artery disease (American Diabetes Association.,2004).
According to the recent national Indian Council of Medical Research - India
ED
Diabetes [ICMR-INDIAB] study currently, in India, there are 62.4 million people with type 2 diabetes mellitus [T2DM] (Anjana et al., 2011). Furthermore, the burden of micro and
PT
macrovascular complications is immense since T2DM occurs at a younger age compared to an occidental population of Europe (Pradeepa et al., 2010). Overall the
CE
prevalence of PAD is lower in Asian Indians, but this is mainly due to the younger age at onset of T2DM. As the population ages, the prevalence of PAD will dramatically
AC
increase. Moreover as India’s population is currently 1.2 billion this means that already there are ~4 million people with PAD assuming the prevalence of PAD to be 6.3% (Premalatha et al., 2000). Indeed it is now known that the economic burden of PAD is equivalent to that of CVD (Mahoney et al., 2010). It is therefore crucial to understand the risk factors for PAD in the Indian diabetic population. Several studies have published information on the prevalence of PAD in the diabetic population. However, only a few studies have reported data on incident PAD or progression of PAD, and there are none from India. Hence the present study was taken up, to assess the prevalence, incidence and progression of, and factors associated with, PAD in Asian Indian T2DM patients attending a large diabetic centre in south India.
ACCEPTED MANUSCRIPT METHODS
T
Study population
RI P
Patients with T2DM, with multiple doppler studies (2001-2011) at the Dr Mohan's Diabetes Specialties Centre, a tertiary diabetes care center in Chennai city in south
SC
India, were included in the study. The centre has state-of-the-art facilities for diabetes and its complications at fifteen clinics in different geographical areas in southern India.
NU
All the clinics are linked through electronic medical records, from which baseline clinical and biochemical characteristics and Ankle Brachial Index [ABI] measurements were
MA
abstracted.
A total of 7,586 T2DM patients aged 20 years and above were registered in
ED
2001, of whom 6893 patients had ABI measurements (response rate 90.9%). Of these, 2512 patients [36.4%] had at least one follow up ABI measurement between the years
PT
2001 and 2011. They were termed ‘responders’ and were included in the study. The rest, i.e., 4,381 of the 6,893 were considered as ‘non-responders’. The mean number of
CE
ABI measurements was 3.6 ± 1.8 during the follow up period and the mean time between first and last ABI was 7.0 ± 2.8 years. There were no significant differences in and the 4,381 non-responders
AC
the baseline values between the 2512 responders
[responders vs non-responders: age (years) 51 10 vs 52 12, p = 0.174; fasting plasma glucose (mg/dl): 160 58 vs 163 58, p = 0.074; duration of diabetes (years) 7.8 6.7 vs 8.0 6.7, p = 0.246; systolic blood pressure (mm Hg): 131 16 vs 132 17, p = 0.128; diastolic blood pressure (mm Hg): 82 7 vs 82 8, p = 0.584)]. The exclusion criteria included patients aged 1.30 was graded as unclassifiable. Progression of PAD was defined as a decrease in ABI>0.15 or a change in category of severity (Hirsch et al., 2006). For
AC
quantitative change the patients were grouped in 3 categories, less than −0.15, −0.15 to +0.15, and more than +0.15. The change in ABI was calculated using the first and last measurements of ABI.
Coronary artery disease [CAD] was diagnosed based on a past history of documented myocardial infarction and/or drug treatment for CAD (aspirin or nitrates) and/or electrocardiographic changes suggestive of ST segment depression and/or Qwave changes and/or T-wave changes using appropriate Minnesota codes (Rose et al., 1982).
Age was defined as the age at the time of the first examination i.e. in 2001.
ACCEPTED MANUSCRIPT Hypertension was diagnosed based on past medical history, drug treatment for hypertension, and/or if the patient had systolic blood pressure [SBP] of 140 mmHg or greater and/or diastolic blood pressure [DBP] of 90 mmHg (National High Blood
RI P
T
Pressure Education Program, 2003) .
Estimated Glomerular Filtration Rate [eGFR] was estimated using the Modification of
SC
Diet in Renal Disease [MDRD] study equation [mL/min/1.73 m2] (Levey et al.,1999 ). The formula used for calculating the GFR was: GFR = 186 × (serum creatinine)−1.154 ×
NU
Age−0.203 × (0.742 if female) × (1.210 if African-American [not applicable to our population])
MA
Smoking: Individuals were classified as ‘never smoked’ and ‘ever smoked’.
ED
Statistical Analysis
All statistical analyses were performed with SAS version 9.1 [SAS Institute, Cary, North
PT
Carolina]. Patients with initial or final ABI values greater than >1.3 were not analyzed for incidence or progression. Baseline characteristics of the population of patients with and
CE
without PAD were compared by logistic regression analysis. Cox proportional hazard models were used to determine the hazard ratio for mortality, incident PAD and
AC
progression. For incident PAD, time was measured from the initial ABI in 2001 to the date of ABI ≤0.9 for incident cases. For mortality, time was measured from the initial ABI to the date of death and date of last visit for censored cases. To build the Cox model, we first did a univariate analysis of each variable .Categorical variables were analyzed with Kaplan-Meir curves to ensure proportionality and the variable was included in the multivariate model if the log rank test had a p-value
