DIAB-6109; No. of Pages 9 diabetes research and clinical practice xxx (2014) xxx–xxx
Contents available at ScienceDirect
Diabetes Research and Clinical Practice journ al h ome pa ge : www .elsevier.co m/lo cate/diabres
Predictors of diabetes foot complications among patients with diabetes in Saudi Arabia Yang Hu a, Balkees A. Bakhotmah b,c, Owiss H. Alzahrani b, Dong Wang e, Frank B. Hu e,f,*, Hasan A. Alzahrani b,d,** a
Division of Rheumatology, Immunology and Allergy, Brigham & Women’s Hospital, Boston, MA, United States The Mohammad Hussein Al Amoudi Chair for Diabetic Foot Research, Jeddah, Saudi Arabia c Department of Nutrition and Food Sciences, Jeddah, Saudi Arabia d Department of Surgery, King Abdulaziz University (KAU), Jeddah, Saudi Arabia e Department of Nutrition and Epidemiology, Harvard School of Public Health, Boston, MA, United States f The Channing Division for Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, United States b
article info
abstract
Article history:
Aims: To identify risk factors and clinical biomarkers of prevalent diabetes foot complica-
Received 1 January 2014
tions, including foot ulcers, gangrene and amputations among patients with diabetes in
Received in revised form
Jeddah, Saudi Arabia.
11 May 2014
Methods: 598 diabetes patients from Jeddah participated in the current study. Patients were
Accepted 21 July 2014
considered to have diabetes foot complications if they reported diagnosis of foot ulcers or
Available online xxx
gangrene or amputations in a questionnaire administered by a physician and confirmed by
Keywords:
by patients, and several clinical markers were assessed following standard procedures.
Diabetes foot complications
Results: The prevalence of diabetes foot complications in this population was 11.4%. In the
clinical exams. Information on socio-demographic and lifestyle variables was self-reported
Foot ulcers
multivariable model without adjustment for PAD (peripheral artery disease) and DPN
Foot gangrene
(diabetes peripheral neuropathy), non-Saudi nationality, longer diabetes duration and
Amputations
insulin use was significantly associated with higher diabetes foot complications prevalence.
Diabetes
Each 1 g/L increase of hemoglobin was associated with 2.8% lower prevalence of diabetes
Saudi Arabia
foot complications. In the multivariable model adjusting for PAD and DPN, the previously observed associations except for nationality were no longer significant. Patients with both DPN and PAD had 9.73 times the odds of diabetes foot complications compared to the patients with neither condition. Conclusion: In this population, longer diabetes duration, insulin use, lower hemoglobin levels and non-Saudi nationality were associated with higher prevalence of foot complications. These associations were largely explained by the presence of DPN and PAD except for non-Saudi nationality. Diabetes patients with both DPN and PAD had nearly 10-fold increased risk of foot complications than those with neither condition. # 2014 Elsevier Ireland Ltd. All rights reserved.
* Corresponding author at: 665 Huntington Avenue, Boston, MA 02115, United States. Tel.: +1 617 432 0113; fax: +1 617 432 2435. ** Corresponding author at: The Vascular Surgery Division, Department of Surgery, King Abdulaziz University (KAU), P.O. Box 80215, Jeddah 21589, Saudi Arabia. Tel.: +966 02 6408346; fax: +966 02 6408346. E-mail addresses: [email protected], [email protected], [email protected] (F.B. Hu), [email protected] (H.A. Alzahrani). http://dx.doi.org/10.1016/j.diabres.2014.07.016 0168-8227/# 2014 Elsevier Ireland Ltd. All rights reserved.
Please cite this article in press as: Hu Y, et al. Predictors of diabetes foot complications among patients with diabetes in Saudi Arabia. Diabetes Res Clin Pract (2014), http://dx.doi.org/10.1016/j.diabres.2014.07.016
DIAB-6109; No. of Pages 9
2
diabetes research and clinical practice xxx (2014) xxx–xxx
1.
Introduction
Diabetes foot complications including foot ulcers, foot gangrene and amputation are among the most serious complications among diabetic patients and cause substantial economical and psychological burden to the patients and society at large. It is estimated that the average lifetime risk of developing foot ulcers among patients with diabetes is 15% [1], and in some populations, the prevalence could be as high as 25% [2]. Ulceration of the foot among patients with diabetes is common, and one study reported 85% of diabetic lower-limb amputations were preceded by non-healing foot ulcers [3]. Some studies reported that patients with chronic foot ulcers had very poor quality of life, which was worsened after amputation [4,5]. Several prospective cohort studies have identified foot insensitivity, history of foot ulcers or amputation, insulin use, Charcot deformity, lower dorsal foot transcutaneous O2 tension, poor vision, orthostatic hypotension, abnormal ankle reflexes and age as independent predictors for incident foot ulcers [6,7]. In addition, longer duration of diabetes, poor glycemic control measured by HbA1c and reduced joint mobility were found to be significant predictors of foot ulcers, although the results are not entirely consistent [6,8,9]. Among these established risk factors, PAD (peripheral artery disease) as reflected by foot ischemia alone with DPN (diabetes peripheral neuropathy) as reflected by impaired peripheral sensation are two most important risk factors that play critical roles in diabetes foot ulcer etiology [2]. According to the latest 2013 International Diabetes Federation report, among the top five Middle Eastern and North African countries for the number of people with diabetes (20– 79 years), Saudi Arabia ranks number 4 with 3.6 million diabetes cases, with the highest diabetes prevalence (23.9%) [10]. The high prevalence of diabetes and accompanying complications leads to a great burden to the health care system and creates a major challenge to diabetes management [11,12]. Therefore, from a public health perspective, it is critical to identify risk factors for foot complications in order to develop preventive strategies [13]. To the best of our knowledge, no previous study has examined risk factors for foot complications in Saudi patients. We therefore conducted this study to investigate the association between demographic, lifestyle, and clinical risk factors and prevalence of diabetes foot complications, including foot ulcers, gangrene, and amputations, in a Saudi population.
2.
Subjects, materials and methods
The study population was recruited by advertisement from Jeddah Governance between June 2009 and May 2010. The inclusion criteria were age of 30 years and older, diagnosed with diabetes for at least 2 years and without current diabetes ulcers. 598 participants were included in the current analysis. The study was approved by the King Abdulaziz University Hospital (KAUH) Ethical Committee. Study protocols, benefits, adverse reactions, and objectives were explained to all participants. Written consent was obtained from all participants. The diagnosis of diabetes mellitus was first self-
reported by patients and then confirmed by physicians through reviewing medical records. Nationality, age, smoking status, personal income level, educational attainment, current medication use and duration of diabetes were self-reported. Nationality was classified as Saudi and non-Saudi. Smoking status was dichotomized as ever smoker and non-smoker. Personal income level was categorized as 10,000 Saudi riyal (SR)/month (1 USD = 3.75 SR). We categorized educational attainment as illiterate, high school, and university. Duration of diabetes was categorized into 20 years. The participant’s body weight was measured to the nearest of 0.1 kg by an electronic weighing scale (Seca, Birmingham, United Kingdom). Height was measured without shoes to the nearest of 0.5 cm by a stadiometer (Seca, Birmingham, United Kingdom). Body mass index (BMI) was calculated as weight (kg) divided by height (m) squared (kg/m2). Waist circumference was measured as the smallest circumference between the rib margin and iliac crest. Blood pressure was measured by an electronic vital signs monitor (Suresigns VS3, Philips medical system, Andover, MA, USA). Two consecutive readings of blood pressure were taken in the right arm of participants in a seated position after 5 min of rest, and the mean of the 2 measures was used for analysis. In the current analysis, participants were considered to have hypertension if they had systolic blood pressure (SBP) 140 mmHg and/or diastolic blood pressure (DBP) 90 mmHg according to the Seventh Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure guidelines [14], and/or using blood-pressure-lowering drugs. DPN was defined as reduced vibration perception and/or reduced light touch perception in either foot of a patient with the following symptoms: loss of sensations, tingling, and deformed foot. Vibration perception was assessed over bony prominences on the dorsal aspect of the 1st and 5th metatarsal heads using the Horwell Neurothesiometer (Scientific Laboratory Supplies, Nottingham, United Kingdom). Reduced vibration perception was defined by a vibration perception threshold 25 V in either foot [15]. Light touch perception was evaluated using a 10-g Semmes-Weinstein monofilament (Huntleigh Diagnostics, Cardiff, United Kingdom) at the plantar aspect of 1st and 5th metatarsal heads [16]. Loss of sensations at these areas in either foot was defined as reduced light touch perception. PAD was diagnosed as ankle–brachial index (ABI) < 0.9. Diagnosis of PAD followed the American College of Cardiology (ACC) and American Heart Association (AHA) Practice Guidelines for the Management of Patients With PAD [17]. All the assessments were conducted by an assessor first and then confirmed by a second assessor independently. Participants were instructed to fast and abstain from vigorous exercise for 12 h prior to medical examination and blood draw. Fasting venous blood samples (10 ml) were taken from the antecubital vein by the laboratory staff and sent to the KAUH’s accredited central laboratory for daily assay. Fasting blood glucose, HbA1c, lipids profile (high-density lipoproteins (HDL), low-density lipoproteins (LDL), triglycerides (TG)), homocysteine, creatinine, high sensitivity C-reactive protein (CRP), serum urea nitrogen, hemoglobin, and complete blood count were measured using standard methods.
Please cite this article in press as: Hu Y, et al. Predictors of diabetes foot complications among patients with diabetes in Saudi Arabia. Diabetes Res Clin Pract (2014), http://dx.doi.org/10.1016/j.diabres.2014.07.016
DIAB-6109; No. of Pages 9
3
diabetes research and clinical practice xxx (2014) xxx–xxx
Because foot gangrene and amputation are usually the ultimate consequences of foot ulcers, we used foot complications as a composite outcome in the current study. Patients were considered to have foot complications if they had one of the following diagnosed conditions: foot ulcer, gangrene and amputation. Patients were considered to have foot ulcer if they reported to have past history of foot ulcer or surgical debridement or have purulent discharge. Patients who reported to have PAD history (color change blackish) or vascular examination were regarded as foot gangrene cases. The identification of foot amputation was based on selfreported toes or mid tarsal amputation or below-knee amputation (BKA) or above-knee amputation (AKA). All categorical variables were presented as number and percentage, and all the continuous variables were shown as mean standard deviation. x2 test with n 1 degree of freedom was used to compare the distribution of categorical variables with n levels between foot complication cases and non-cases. Two-sample t-test with equal or unequal variance was used to compare the continuous variables between foot complication cases and non-cases. We employed a 2-step method for variable selection. First, we used multivariable logistic regression to estimate the odds ratio and 95% confidence interval (CI) between each risk factor and risk of foot complications with adjustment for age, sex and nationality. Second, variables that reached significant level of 0.10 were included into the final model. To assess whether selected variables were associated with the risk of foot complications independent of DPN and PAD, 2 separate models were run: one without adjustment for DPN and PAD and the other adjusted for the two conditions. Since both DPN and PAD were strong predictors of foot complications, we quantified the odds ratio of foot complications according to the presence of PAD and DPN among patients with diabetes: no DPN and PAD, PAD and no DPN, and both DPN and PAD. Continuous variables were included in all models as quartiles, and the p for trend was estimated from the linear trend test using the median value of each category. All statistical analysis was conducted using SAS 9.3 software (SAS Institute, Cary, NC). All P values were 2-tailed (a = 0.05).
3.
Results
Table 1 shows the distribution of foot ulcers, gangrene, amputations and total foot complications according to sex and age groups. Among 598 participants, 11.4% of the patients had diagnosed foot complications. The prevalence of foot ulcers, gangrene and amputations were 7.9%, 1.8% and 3.5% respectively. The prevalence of each outcome was similar between males and females, and the prevalence tended to increase with age. The characteristics of the patients organized according to foot complication status are presented in Table 2. There were significantly more foot complications cases among non-Saudi nationalities, insulin users and Clopidogrel users. Moreover, patients with foot complications were more likely to be older, have lower income, have longer diabetes duration and have lower hemoglobin levels. The association between each risk factor and prevalence of foot complications is shown in Table 3. Diabetes duration (OR20+vs.2–5years = 10.09, 95% CI: 3.51–28.94) and insulin use (OR = 3.60, 95% CI: 2.10–6.17) were significantly associated with increased risk of foot complications, while oral hypoglycemic drug use (OR = 0.45, 95% CI: 0.25–0.81) and hemoglobin levels (ORQ4vs.Q1 = 0.23, 95% CI: 0.08–0.64, P for trend 0.005) were inversely associated with foot complications. The significant predictors from Table 3 were mutually adjusted in 2 separate multivariable logistic models. The results are shown in Table 4. In the model without adjustment for DPN and PAD, non-Saudi nationality (OR = 2.80, 95% CI: 1.61–4.85), insulin use (OR = 2.10, 95% CI: 1.08–4.09), and diabetes duration (OR20+vs.2–5years = 5.70, 95% CI: 1.80–18.11) were independently and significantly associated with higher odds of foot complications, whereas higher hemoglobin levels (ORQ4vs.Q1 = 0.31, 95% CI: 0.11–0.89, P for trend 0.024) were associated with reduced odds of foot complications. In the model adjusting for DPN and PAD, the associations for insulin use, diabetes duration and hemoglobin level were no longer significant. Patients with DPN had 3.21 times (OR = 3.21, 95% CI: 1.69–6.10) the odds of foot complications than those without the condition, and patients with PAD had nearly 3 fold
Table 1 – Distribution of foot ulcers, gangrene, amputations and total foot complications according to age and sex.a Gender Male Foot ulcer 342 (92.2) No 29 (7.8) Yes Foot gangrene No 363 (97.8) 8 (2.2) Yes Foot amputation 357 (96.2) No 14 (3.8) Yes Foot complicationsb No 330 (88.9) 41 (11.1) Yes a b
Age (years)
Total
Female
45
45.1–55
55.1–65
>65.0
209 (92.1) 18 (7.9)
118 (95.9) 5 (4.1)
232 (91.7) 21 (8.3)
140 (90.9) 14 (9.1)
61 (89.7) 7 (10.3)
551 (92.1) 47 (7.9)
224 (98.7) 3 (1.3)
122 (99.2) 1 (0.8)
247 (97.6) 6 (2.4)
151 (98.1) 3 (1.9)
67 (98.5) 1 (1.5)
587 (98.2) 11 (1.8)
220 (96.9) 7 (3.1)
119 (96.7) 4 (3.3)
248 (98.0) 5 (2.0)
148 (96.1) 6 (3.9)
62 (91.2) 6 (8.8)
577 (96.5) 21 (3.5)
200 (88.1) 27 (11.9)
114 (92.6) 9 (7.4)
224 (88.5) 29 (11.5)
133 (86.4) 21 (13.6)
59 (86.8) 9 (13.2)
530 (88.6) 68 (11.4)
n (%) for all such values. Foot complications include foot ulcers, foot gangrene, and foot amputations.
Please cite this article in press as: Hu Y, et al. Predictors of diabetes foot complications among patients with diabetes in Saudi Arabia. Diabetes Res Clin Pract (2014), http://dx.doi.org/10.1016/j.diabres.2014.07.016
DIAB-6109; No. of Pages 9
4
diabetes research and clinical practice xxx (2014) xxx–xxx
Table 2 – Characteristics of 598 participants according to foot complications status. Foot complication cases
Pa
330 (62.3) 200 (37.7) 503 (94.9)
41 (60.3) 42 (61.8) 64 (94.1)
0.753
Contents available at ScienceDirect
Diabetes Research and Clinical Practice journ al h ome pa ge : www .elsevier.co m/lo cate/diabres
Predictors of diabetes foot complications among patients with diabetes in Saudi Arabia Yang Hu a, Balkees A. Bakhotmah b,c, Owiss H. Alzahrani b, Dong Wang e, Frank B. Hu e,f,*, Hasan A. Alzahrani b,d,** a
Division of Rheumatology, Immunology and Allergy, Brigham & Women’s Hospital, Boston, MA, United States The Mohammad Hussein Al Amoudi Chair for Diabetic Foot Research, Jeddah, Saudi Arabia c Department of Nutrition and Food Sciences, Jeddah, Saudi Arabia d Department of Surgery, King Abdulaziz University (KAU), Jeddah, Saudi Arabia e Department of Nutrition and Epidemiology, Harvard School of Public Health, Boston, MA, United States f The Channing Division for Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, United States b
article info
abstract
Article history:
Aims: To identify risk factors and clinical biomarkers of prevalent diabetes foot complica-
Received 1 January 2014
tions, including foot ulcers, gangrene and amputations among patients with diabetes in
Received in revised form
Jeddah, Saudi Arabia.
11 May 2014
Methods: 598 diabetes patients from Jeddah participated in the current study. Patients were
Accepted 21 July 2014
considered to have diabetes foot complications if they reported diagnosis of foot ulcers or
Available online xxx
gangrene or amputations in a questionnaire administered by a physician and confirmed by
Keywords:
by patients, and several clinical markers were assessed following standard procedures.
Diabetes foot complications
Results: The prevalence of diabetes foot complications in this population was 11.4%. In the
clinical exams. Information on socio-demographic and lifestyle variables was self-reported
Foot ulcers
multivariable model without adjustment for PAD (peripheral artery disease) and DPN
Foot gangrene
(diabetes peripheral neuropathy), non-Saudi nationality, longer diabetes duration and
Amputations
insulin use was significantly associated with higher diabetes foot complications prevalence.
Diabetes
Each 1 g/L increase of hemoglobin was associated with 2.8% lower prevalence of diabetes
Saudi Arabia
foot complications. In the multivariable model adjusting for PAD and DPN, the previously observed associations except for nationality were no longer significant. Patients with both DPN and PAD had 9.73 times the odds of diabetes foot complications compared to the patients with neither condition. Conclusion: In this population, longer diabetes duration, insulin use, lower hemoglobin levels and non-Saudi nationality were associated with higher prevalence of foot complications. These associations were largely explained by the presence of DPN and PAD except for non-Saudi nationality. Diabetes patients with both DPN and PAD had nearly 10-fold increased risk of foot complications than those with neither condition. # 2014 Elsevier Ireland Ltd. All rights reserved.
* Corresponding author at: 665 Huntington Avenue, Boston, MA 02115, United States. Tel.: +1 617 432 0113; fax: +1 617 432 2435. ** Corresponding author at: The Vascular Surgery Division, Department of Surgery, King Abdulaziz University (KAU), P.O. Box 80215, Jeddah 21589, Saudi Arabia. Tel.: +966 02 6408346; fax: +966 02 6408346. E-mail addresses: [email protected], [email protected], [email protected] (F.B. Hu), [email protected] (H.A. Alzahrani). http://dx.doi.org/10.1016/j.diabres.2014.07.016 0168-8227/# 2014 Elsevier Ireland Ltd. All rights reserved.
Please cite this article in press as: Hu Y, et al. Predictors of diabetes foot complications among patients with diabetes in Saudi Arabia. Diabetes Res Clin Pract (2014), http://dx.doi.org/10.1016/j.diabres.2014.07.016
DIAB-6109; No. of Pages 9
2
diabetes research and clinical practice xxx (2014) xxx–xxx
1.
Introduction
Diabetes foot complications including foot ulcers, foot gangrene and amputation are among the most serious complications among diabetic patients and cause substantial economical and psychological burden to the patients and society at large. It is estimated that the average lifetime risk of developing foot ulcers among patients with diabetes is 15% [1], and in some populations, the prevalence could be as high as 25% [2]. Ulceration of the foot among patients with diabetes is common, and one study reported 85% of diabetic lower-limb amputations were preceded by non-healing foot ulcers [3]. Some studies reported that patients with chronic foot ulcers had very poor quality of life, which was worsened after amputation [4,5]. Several prospective cohort studies have identified foot insensitivity, history of foot ulcers or amputation, insulin use, Charcot deformity, lower dorsal foot transcutaneous O2 tension, poor vision, orthostatic hypotension, abnormal ankle reflexes and age as independent predictors for incident foot ulcers [6,7]. In addition, longer duration of diabetes, poor glycemic control measured by HbA1c and reduced joint mobility were found to be significant predictors of foot ulcers, although the results are not entirely consistent [6,8,9]. Among these established risk factors, PAD (peripheral artery disease) as reflected by foot ischemia alone with DPN (diabetes peripheral neuropathy) as reflected by impaired peripheral sensation are two most important risk factors that play critical roles in diabetes foot ulcer etiology [2]. According to the latest 2013 International Diabetes Federation report, among the top five Middle Eastern and North African countries for the number of people with diabetes (20– 79 years), Saudi Arabia ranks number 4 with 3.6 million diabetes cases, with the highest diabetes prevalence (23.9%) [10]. The high prevalence of diabetes and accompanying complications leads to a great burden to the health care system and creates a major challenge to diabetes management [11,12]. Therefore, from a public health perspective, it is critical to identify risk factors for foot complications in order to develop preventive strategies [13]. To the best of our knowledge, no previous study has examined risk factors for foot complications in Saudi patients. We therefore conducted this study to investigate the association between demographic, lifestyle, and clinical risk factors and prevalence of diabetes foot complications, including foot ulcers, gangrene, and amputations, in a Saudi population.
2.
Subjects, materials and methods
The study population was recruited by advertisement from Jeddah Governance between June 2009 and May 2010. The inclusion criteria were age of 30 years and older, diagnosed with diabetes for at least 2 years and without current diabetes ulcers. 598 participants were included in the current analysis. The study was approved by the King Abdulaziz University Hospital (KAUH) Ethical Committee. Study protocols, benefits, adverse reactions, and objectives were explained to all participants. Written consent was obtained from all participants. The diagnosis of diabetes mellitus was first self-
reported by patients and then confirmed by physicians through reviewing medical records. Nationality, age, smoking status, personal income level, educational attainment, current medication use and duration of diabetes were self-reported. Nationality was classified as Saudi and non-Saudi. Smoking status was dichotomized as ever smoker and non-smoker. Personal income level was categorized as 10,000 Saudi riyal (SR)/month (1 USD = 3.75 SR). We categorized educational attainment as illiterate, high school, and university. Duration of diabetes was categorized into 20 years. The participant’s body weight was measured to the nearest of 0.1 kg by an electronic weighing scale (Seca, Birmingham, United Kingdom). Height was measured without shoes to the nearest of 0.5 cm by a stadiometer (Seca, Birmingham, United Kingdom). Body mass index (BMI) was calculated as weight (kg) divided by height (m) squared (kg/m2). Waist circumference was measured as the smallest circumference between the rib margin and iliac crest. Blood pressure was measured by an electronic vital signs monitor (Suresigns VS3, Philips medical system, Andover, MA, USA). Two consecutive readings of blood pressure were taken in the right arm of participants in a seated position after 5 min of rest, and the mean of the 2 measures was used for analysis. In the current analysis, participants were considered to have hypertension if they had systolic blood pressure (SBP) 140 mmHg and/or diastolic blood pressure (DBP) 90 mmHg according to the Seventh Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure guidelines [14], and/or using blood-pressure-lowering drugs. DPN was defined as reduced vibration perception and/or reduced light touch perception in either foot of a patient with the following symptoms: loss of sensations, tingling, and deformed foot. Vibration perception was assessed over bony prominences on the dorsal aspect of the 1st and 5th metatarsal heads using the Horwell Neurothesiometer (Scientific Laboratory Supplies, Nottingham, United Kingdom). Reduced vibration perception was defined by a vibration perception threshold 25 V in either foot [15]. Light touch perception was evaluated using a 10-g Semmes-Weinstein monofilament (Huntleigh Diagnostics, Cardiff, United Kingdom) at the plantar aspect of 1st and 5th metatarsal heads [16]. Loss of sensations at these areas in either foot was defined as reduced light touch perception. PAD was diagnosed as ankle–brachial index (ABI) < 0.9. Diagnosis of PAD followed the American College of Cardiology (ACC) and American Heart Association (AHA) Practice Guidelines for the Management of Patients With PAD [17]. All the assessments were conducted by an assessor first and then confirmed by a second assessor independently. Participants were instructed to fast and abstain from vigorous exercise for 12 h prior to medical examination and blood draw. Fasting venous blood samples (10 ml) were taken from the antecubital vein by the laboratory staff and sent to the KAUH’s accredited central laboratory for daily assay. Fasting blood glucose, HbA1c, lipids profile (high-density lipoproteins (HDL), low-density lipoproteins (LDL), triglycerides (TG)), homocysteine, creatinine, high sensitivity C-reactive protein (CRP), serum urea nitrogen, hemoglobin, and complete blood count were measured using standard methods.
Please cite this article in press as: Hu Y, et al. Predictors of diabetes foot complications among patients with diabetes in Saudi Arabia. Diabetes Res Clin Pract (2014), http://dx.doi.org/10.1016/j.diabres.2014.07.016
DIAB-6109; No. of Pages 9
3
diabetes research and clinical practice xxx (2014) xxx–xxx
Because foot gangrene and amputation are usually the ultimate consequences of foot ulcers, we used foot complications as a composite outcome in the current study. Patients were considered to have foot complications if they had one of the following diagnosed conditions: foot ulcer, gangrene and amputation. Patients were considered to have foot ulcer if they reported to have past history of foot ulcer or surgical debridement or have purulent discharge. Patients who reported to have PAD history (color change blackish) or vascular examination were regarded as foot gangrene cases. The identification of foot amputation was based on selfreported toes or mid tarsal amputation or below-knee amputation (BKA) or above-knee amputation (AKA). All categorical variables were presented as number and percentage, and all the continuous variables were shown as mean standard deviation. x2 test with n 1 degree of freedom was used to compare the distribution of categorical variables with n levels between foot complication cases and non-cases. Two-sample t-test with equal or unequal variance was used to compare the continuous variables between foot complication cases and non-cases. We employed a 2-step method for variable selection. First, we used multivariable logistic regression to estimate the odds ratio and 95% confidence interval (CI) between each risk factor and risk of foot complications with adjustment for age, sex and nationality. Second, variables that reached significant level of 0.10 were included into the final model. To assess whether selected variables were associated with the risk of foot complications independent of DPN and PAD, 2 separate models were run: one without adjustment for DPN and PAD and the other adjusted for the two conditions. Since both DPN and PAD were strong predictors of foot complications, we quantified the odds ratio of foot complications according to the presence of PAD and DPN among patients with diabetes: no DPN and PAD, PAD and no DPN, and both DPN and PAD. Continuous variables were included in all models as quartiles, and the p for trend was estimated from the linear trend test using the median value of each category. All statistical analysis was conducted using SAS 9.3 software (SAS Institute, Cary, NC). All P values were 2-tailed (a = 0.05).
3.
Results
Table 1 shows the distribution of foot ulcers, gangrene, amputations and total foot complications according to sex and age groups. Among 598 participants, 11.4% of the patients had diagnosed foot complications. The prevalence of foot ulcers, gangrene and amputations were 7.9%, 1.8% and 3.5% respectively. The prevalence of each outcome was similar between males and females, and the prevalence tended to increase with age. The characteristics of the patients organized according to foot complication status are presented in Table 2. There were significantly more foot complications cases among non-Saudi nationalities, insulin users and Clopidogrel users. Moreover, patients with foot complications were more likely to be older, have lower income, have longer diabetes duration and have lower hemoglobin levels. The association between each risk factor and prevalence of foot complications is shown in Table 3. Diabetes duration (OR20+vs.2–5years = 10.09, 95% CI: 3.51–28.94) and insulin use (OR = 3.60, 95% CI: 2.10–6.17) were significantly associated with increased risk of foot complications, while oral hypoglycemic drug use (OR = 0.45, 95% CI: 0.25–0.81) and hemoglobin levels (ORQ4vs.Q1 = 0.23, 95% CI: 0.08–0.64, P for trend 0.005) were inversely associated with foot complications. The significant predictors from Table 3 were mutually adjusted in 2 separate multivariable logistic models. The results are shown in Table 4. In the model without adjustment for DPN and PAD, non-Saudi nationality (OR = 2.80, 95% CI: 1.61–4.85), insulin use (OR = 2.10, 95% CI: 1.08–4.09), and diabetes duration (OR20+vs.2–5years = 5.70, 95% CI: 1.80–18.11) were independently and significantly associated with higher odds of foot complications, whereas higher hemoglobin levels (ORQ4vs.Q1 = 0.31, 95% CI: 0.11–0.89, P for trend 0.024) were associated with reduced odds of foot complications. In the model adjusting for DPN and PAD, the associations for insulin use, diabetes duration and hemoglobin level were no longer significant. Patients with DPN had 3.21 times (OR = 3.21, 95% CI: 1.69–6.10) the odds of foot complications than those without the condition, and patients with PAD had nearly 3 fold
Table 1 – Distribution of foot ulcers, gangrene, amputations and total foot complications according to age and sex.a Gender Male Foot ulcer 342 (92.2) No 29 (7.8) Yes Foot gangrene No 363 (97.8) 8 (2.2) Yes Foot amputation 357 (96.2) No 14 (3.8) Yes Foot complicationsb No 330 (88.9) 41 (11.1) Yes a b
Age (years)
Total
Female
45
45.1–55
55.1–65
>65.0
209 (92.1) 18 (7.9)
118 (95.9) 5 (4.1)
232 (91.7) 21 (8.3)
140 (90.9) 14 (9.1)
61 (89.7) 7 (10.3)
551 (92.1) 47 (7.9)
224 (98.7) 3 (1.3)
122 (99.2) 1 (0.8)
247 (97.6) 6 (2.4)
151 (98.1) 3 (1.9)
67 (98.5) 1 (1.5)
587 (98.2) 11 (1.8)
220 (96.9) 7 (3.1)
119 (96.7) 4 (3.3)
248 (98.0) 5 (2.0)
148 (96.1) 6 (3.9)
62 (91.2) 6 (8.8)
577 (96.5) 21 (3.5)
200 (88.1) 27 (11.9)
114 (92.6) 9 (7.4)
224 (88.5) 29 (11.5)
133 (86.4) 21 (13.6)
59 (86.8) 9 (13.2)
530 (88.6) 68 (11.4)
n (%) for all such values. Foot complications include foot ulcers, foot gangrene, and foot amputations.
Please cite this article in press as: Hu Y, et al. Predictors of diabetes foot complications among patients with diabetes in Saudi Arabia. Diabetes Res Clin Pract (2014), http://dx.doi.org/10.1016/j.diabres.2014.07.016
DIAB-6109; No. of Pages 9
4
diabetes research and clinical practice xxx (2014) xxx–xxx
Table 2 – Characteristics of 598 participants according to foot complications status. Foot complication cases
Pa
330 (62.3) 200 (37.7) 503 (94.9)
41 (60.3) 42 (61.8) 64 (94.1)
0.753
