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Prevalence and Risk Factors for Diabetic Peripheral Neuropathy Among Saudi Hospitalized Diabetic Patients: A Nested Case-Control Study

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ORIGINAL RESEARCH
Prevalence and Risk Factors for Diabetic
Peripheral Neuropathy Among Saudi Hospitalized
Diabetic Patients: A Nested Case-Control Study
This article was published in the following Dove Press journal:
International Journal of General Medicine
Fahad AS Aleidan
1,2
Banderi A Ahmad
1
Farah A Alotaibi
1
Dalal H Aleesa
1
Nuha A Alhefdhi
1
Motasim Badri
1
Abdel Galil Abdel Gader
1
1
College of Medicine, King Saud Bin
Abdulaziz University for Health Sciences,
Riyadh, Saudi Arabia;
2
College of
Medicine, King Abdulaziz Medical City,
Riyadh, Saudi Arabia
Objective: To determine the prevalence and the risk factors of diabetic peripheral neuro-
pathy (DPN) in hospitalized adult Saudi diabetics.
Methods: This is a retrospective, nested case-control study conducted at King Abdulaziz
Medical City (KAMC) in Riyadh, Saudi Arabia. All diabetic patients admitted to the hospital
between the January 1, and December 31, 2018 were considered for inclusion in the study.
Patients with DPN were identied and three controls per case were randomly selected from
the remaining diabetic patients without peripheral neuropathy (PN).
Results: A total of 2,096 adult diabetic patients were identied during the study period. Of
these, 73 patients (3.5%) were conrmed to be suffering from DPN and 219 were included as
controls. When comparing diabetic with the control cases, DPN cases were signicantly
older (p=0.002), had a signicantly higher proportion of type 2 diabetes (p=0.023), chronic
kidney disease (p<0.0001), cerebral vascular stroke (p=0.027), hypertension (p=0.005),
dyslipidemia (p=0.002), peripheral vascular disease (p<0.0001), osteoarthritis (p=0.034),
diabetic ketoacidosis (p=0.003), foot ulcers (p=0.006), gangrene (p=0.001), lower limb
ischemia (p=0.001), increased duration with diabetic disease (p=0.031), increased BMI
(p=0.003), higher serum creatinine (p<0.001) and lower serum albumin levels (p=0.035).
In the multivariate logistic regression, only older age {odds ratio (OR) 1.02, 95% CI 1.01–
1.04, p=0.031}, chronic kidney disease (OR 2.39, 95% CI 1.23–4.64, p=0.010) and periph-
eral vascular disease (OR 3.14, 95% CI 1.39–7.13, p=0.006) were independently associated
with DPN.
Conclusion: This study identied several risk factors that contributed to the development of
DPN in Saudis. These must be considered in strategies and campaigns aimed at risk
reduction of cardiovascular and chronic diseases, and consequently progression of DPN.
Keywords: diabetes mellitus, diabetic peripheral neuropathy, risk factors
Introduction
Diabetic peripheral neuropathy DPN is dened as, “the presence of symptoms and/
or signs of peripheral nerve dysfunction in patients with diabetes after the exclusion
of other causes,” and may be present despite a lack of symptoms.
1
The diagnosis
relies on clinical signs as well as quantitative electrophysiological testing:
1
DPN is
a common complication in patients with diabetes and its consequences can be
distressing, as patients may develop neuropathic feet pain and decreased sensation
that can lead to frequent falls and injuries. Patients may also develop foot ulcers.
All these consequences of DPN will unavoidably end in the reduction in the quality
Correspondence: Fahad AS Aleidan
College of Medicine, King Saud Bin
Abdulaziz University for Health Sciences,
Riyadh, Saudi Arabia
Tel +966118011111
Email faleidan@yahoo.com
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of life and signicant economic burden both to the patients
and society.
25
Although up to 50% of patients with DPN
are asymptomatic, some patients may manifest burning
feet pain, due to progressive sensory impairment, which
responds poorly to analgesics. Rarely, this sensory impair-
ment could lead to foot ulceration and eventually to lower
limb amputation;
6,7
diabetes is a leading cause of “non-
traumatic” lower limb amputation.
8
There is wide agreement that DPN is a consequence of
diabetes longstanding hyperglycemia which is critical for
peripheral nerve damage and distal-predominant nerve
ber degeneration.
911
The chronic diabetes hyperglyce-
mia is compounded by numerous metabolic aberrations
and diabetic microvascular complications resulting from
disturbed nutritional support especially of the most distal
parts of very long nerve axons originating in the spinal
cord and travel long distances to supply the lower limbs
and the feet, in particular. Additionally, the sparse vascular
supply in this area, resulting from diabetes, is likely to
cause further hypoxic nerve damage. Other confounding
metabolic aberrations resulting from chronic hypoglyce-
mia include the excessive release of cytokines, and exag-
gerated oxidative stress. This topic has been reviewed in
detail elsewhere.
9
Although diabetes is considered the
main underlying cause of DPN, the pre-diabetic stage
with other comorbidities such as: obesity, hypertension
and hyperlipidemia may increase the risk of neuropathy.-
1215
Moreover, treatment modalities received by diabetic
patients (insulin and/or oral hypoglycemic agents) play an
additional important role in delaying the development of
this complication among diabetic patients. A meta-analysis
conducted on 1,228 patients with type 1 diabetes and
6,669 patients with type 2 diabetes revealed signicant
reduction of neuropathy when blood sugar is controlled
within the limits of normal.
13
Type 2 diabetes mellitus is becoming a rapidly growing
health problem in the afuent oil rich Gulf Council states
(Saudi Arabia, Oman, Kuwait, Bahrain, and the United
Arab Emirates). Its prevalence is highest in Saudi Arabia
(31.6%, 29.0%.25.4%. 25.0%, 25.0%, and 16.7%,
respectively).
16
This high prevalence of type 2 diabetes
was found to be signicantly associated with the high
Gross Domestic Product (GDP) and energy consumption.
In contrast the lowest prevalence was found in the poorest
Arab countries (Mauritania, 4.7% and Somalia, 3.9%).
Careful search in the literature uncovered only two
small studies on painful DPN undertaken in different pri-
mary health facilities.
17,18
The rst study
17
which was
undertaken in a Primary Health Centre (PHC) in Riyadh
found 35% of patients with type-2 diabetes (n =242)
suffering from DPN. On the other hand, the second study
18
which was also a PHC study found the prevalence of DPN
to be 30.1% (n = 235). With this alarming prevalence of
DPN in Saudi diabetics we felt the need to have better
documentation of DPN. Thus, the aim of the current study
was to determine the prevalence and risk factors associated
with the development of DPN in a large population of
hospitalized adult Saudi diabetics.
Methods
This is a retrospective, nested case-control study con-
ducted at King Abdulaziz Medical City (KAMC); a ter-
tiary health care facility in Riyadh, Saudi Arabia. All adult
patients, who were admitted with diabetes mellitus at
KAMC, during the study period (from January 1 to
December 31, 2018) were considered for inclusion in the
study. Additionally, they met the ADA diagnosis criteria
(fasting blood glucose ≥7.0 mmol/L, glycosylated hemo-
globin [HbA1C] ≥6.5%, classic symptoms of hyperglyce-
mia, hyperglycemic crisis with a random plasma glucose
≥11.1 mmol/L or 2-hour plasma glucose ≥11.11 mmol/L).
Of these, patients with conrmed DPN diagnosis were
identied and served as case patients. Whereas, three con-
trols per case were randomly selected from the remaining
diabetic patients without peripheral neuropathy (PN).
Patients who were under the age of 18 or did not fulll
the eligibility criteria were not considered for participation
in the study.
19
DPN conrmation was based on the follow-
ing criteria: 1) abnormal clinical examination for pain,
touch, vibration, pressure, power, and ankle reex; and
2) abnormal nerve conduction studies (NCS) and/or
electromyography.
Medical records of all enrolled patients (cases and
controls) were accessed and the collected data were
recorded in computerized format. These data included:
demographic characteristics: age, gender, body mass
index (BMI), type of diabetes, presence and duration of
diabetic neuropathy, hypertension, kidney disease, dyslipi-
demia, and other comorbidities, life style (smoking and
alcohol use), blood biochemistry indices (fasting blood
glucose, HbA1C, lipid prole), medications, particularly
insulin, oral hypoglycemic agents and diet, blood pressure
and other clinical complications.
All methods and procedures were performed in accor-
dance with the relevant institutional guidelines and regula-
tions. The study was approved by the Institutional Review
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Board at King Abdullah International Medical Research
Center (KAIMRC). The ethical committee waived the
need for written informed consent due to the retrospective
nature of the study.
Statistical Analysis
Data were analyzed using the Statistical Package for the
Social Sciences Program (IBM SPSS Statistics version
24). Continuous data were presented as medians (inter-
quartile range), and categorical data as frequencies (%).
Data were compared using Mann–Whitney U-test or χ
2
-
test; as appropriate. Conditional logistic regression analy-
sis was conducted to identify the factors associated with
the DPN. Factors found statistically signicant in logistic
univariate analyses were included in the nal multivariate
model. Strength of the association was expressed as odds
ratios (OR) with 95% condence interval. All tests were
two-sided and a p-value less than 0.05 was considered
statistically signicant.
Results
A total of 2,906 patients with diabetes were identied
during the study period. Of these, 73 patients (3.5%)
were found and labeled in the electronic chart by the
treating clinician with DPN and 219 patients (three to
one DPN case) were randomly selected as a control
group. Table 1 shows the basic characteristics of the
two groups. Females represented 51.8% and 63.0% of
the DPN and the controls, respectively. The median
(IQR) age of patients in the DPN group was signi-
cantly higher than in the controls [65 (58–75) vs 61
(45–71), p=0.002)] and the duration of diabetes of
patients with DPN was signicantly higher than in the
controls [8.5 (5.5–16) vs 6.5 (4–15), p=0.031]. Type 2
DM was diagnosed in 66 (90.4%) patients with DPN,
compared with 173 (78.6%) patients in the control
group, and 7 (9.6%) patients with DPN were diagnosed
with type 1 DM compared with 47 (21.4%) patients in
the control group. The median BMI of patients with
DPN was signicantly higher than controls [31 (26–
35) vs 27 (22–33), p=0.003]. However, the two groups
were similar in gender distribution (p=0.096), treatment
modalities (p=0.072), smoking status (p=0.131) and
alcohol consumption (p=0.413). Biochemical indices
and assessment parameters were also similar in both
groups (Table 1).
The median number of comorbidities in DPN patients
was signicantly higher than in controls [5(4–7.5) vs 4 (2–
5.75), p<0.001]. Hypertension was more prevalent in the
DPN patients (p=0.005); so were peripheral vascular dis-
ease (p<0.001), cerebral vascular accident (p=0.027),
chronic kidney disease (p<0.001) and dyslipidemia
(p=0.002), than in control patients. Other comorbid dis-
eases were similar in both groups. The DPN patients
developed diabetic complications more than the control
patients (Table 2).
Table 3 shows the results of the nal multivariate
logistic regression for factors associated with DPN. The
independent factors associated with the likelihood of DPN
were age (OR 1.02, 95% CI 1.01–1.05, p=0.031), periph-
eral vascular disease (OR 3.14, 95% CI 1.39–7.127,
p=0.006) and chronic kidney disease (OR 2.39, 95% CI
1.23–4.64, p=0.010). However, the presence of hyperten-
sion, cerebral vascular disease and dyslipidemia were not
signicantly associated with DPN.
Discussion
DPN is a very distressing chronic complication of diabetes
with an array of poor outcomes. For example, DPN leads to
neuropathic pain and diminished sensation which in turn can
lead to frequent falls and injuries, restriction of movement,
poor quality of life and difculties with earning a living. Other
serious complications include: leg ulcers that can eventually
end in leg amputation.
15,20,21
DPN is classied into numerous types and subtypes
based on a mixture of phenomenological, aetiological, patho-
logical and neurophysiological parameters.
1,2224
In a retro-
spective study, like the present one, it is difcult to assure the
reliability of information on the details of these types or
subtypes and be condent that such information has been
documented in every patient. Accordingly, we restricted the
denition of DPN, as mentioned earlier, to the presence of
symptoms and/or signs of peripheral nerve dysfunction in
patients with diabetes after the exclusion of other causes.
1
Interest in DPN stems from the fact that it has recently
been recognized as the most common of all the neuropathy
complications worldwide.
25
However, the reported preva-
lence of DPN varies widely from study to study and is
heavily dependent on the type of diabetes, the population
selected, and criteria used for dening cases, including the
degree of control of the hyperglycemia.
26
The most clas-
sical citation of DPN is a study conducted in France
27
in
which 4,400 adults with diabetes were followed for 36
years (1937–1973). Approximately 50% of these patients
developed DPN at the end of the follow-up period. Pirart
27
found that two thirds of patients with diabetes had
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objective evidence of some form of neuropathy. The most
common was DPN; affecting 50% of type 2 diabetics.
Outside Europe, particularly in Asia and Africa, a very
wide range of prevalences were reported. For examples
Saudi Arabia (19.9; n = 552);
28
Turkey (60%; n = 550),
29
China: (61.8%, n = 435);
30
and Tanzania (72.2%, n =
327).
31
On the other hand, recent studies from Europe
and the US have reported prevalences ranging from 6%
to 51% depending on the population studied.
1
We noted
that the frequency of DPN in our patients was consider-
ably lower than expected. This maybe owing to the fact
that, typically, DPN is often diagnosed clinically with little
further laboratory investigations to conrm the diagnosis
or poorly captured in patients’ records. In a study by Day
et al,
32
more than 40% of diabetic patients in general
practice had no biochemical evaluation, eye or foot
examination.
32
The wide geographical variations in prevalence of
DPN highlight the need for a global multicenter study in
which the selection criteria for diabetic patients are unied
to the nest detail. Hopefully, then, the true reection of
the geographical and ethnic differences in the prevalence
of DPN can be meaningful and may shed some light in the
mechanism underlying the differences in the prevalences
in the DPN in different ethnic groups.
This possibility proved to be true in a comparative
study between South Asians and Caucasians living in
Britain where the prevalence of DPN was found to be
signicantly lower in South Asians (38.1%) than White
Caucasians (54.3%). Further observations uncovered
Table 1 Clinical and Demographic Characteristics of the DPN and Control Patients
Variables Control
(n=220)
DPN
(n=73)
p-value
Age, years (median, IQR) 61 (45–71) 65 (58–75) 0.002
Gender, n (%) 0.096
Male 106 (48.2) 27 (37.0)
Female 114 (51.8) 46 (63.0)
Duration of diabetes years, median (IQR) 6.5 (4–15) 8.5 (5.5–16) 0.031
Type of DM, n (%) 0.025
Type I 47 (21.4) 7 (9.6)
Type II 173 (78.6) 66 (90.4)
Type of treatment, n (%) 0.072
Insulin 158 (72.8) 62 (86.1)
Oral hypoglycemic 53 (24.4) 9 (12.5)
Diet 6 (2.8) 1 (1.4)
BMI kg/cm
2
, median (IQR) 27 (22–33) 31 (26–35) 0.003
Smoking status 29 (13.2) 15 (20.5) 0.131
Alcohol status 2 (0.9) 0 (0.0) 0.413
Laboratory indices
Fasting blood glucose mmol/L (median, IQR) 9 (7–12) 10 (6–14) 0.507
HbA1C (median, IQR) 9 (7–10) 9 (7–10) 0.851
Systolic blood pressure mmHg (median, IQR) 124 (107–139) 125 (110–143) 0.254
Diastolic blood pressure mmHg (median, IQR) 69 (58–76) 66 (55–73) 0.158
Micro-albuminuria (median, IQR) 26 (2–100) 50 (50–200) 0.092
Proteinuria (median, IQR) 2 (1.25–2) 2 (1–2) 0.218
Serum Creatinine umol/L (median, IQR) 71 (61–117) 103 (80–192.5) <0.001
Cholesterol mmol/L (median, IQR) 4 (3–5) 4 (3–4.75) 0.649
Triglycerides mmol/L (median, IQR) 1(1–2) 1 (1–2) 0.356
Albumin g/L (median, IQR) 37 (32–40) 35 (30–39) 0.035
Abbreviations: BMI, body mass index; DPN, diabetes peripheral neuropathy; IQR, interquartile range.
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foot insensitivity as assessed by 10 g monolament
perception, was more common in Caucasians (43.9%
vs 23.8%). South Asians have better preserved small
nerve ber integrity than equivalent Europeans.
Corneal nerve ber length (22.0 ± 7.9 vs 19.3 ± 6.3
mm/mm
2
), corneal nerve branch density [(geometric
mean (range): 60.0 (4.7–246.2) vs 46.0 (3.1–129.2)
no./mm
2
], and heart rate variability [(geometric mean
Table 2 Associated Comorbidities and Diabetes Complications
Variables Control
(n=220)
DPN
(n=73)
p-value
Number of comorbid disease (median, IQR) 4 (2–5.75) 5 (4–7.5) <0.001
Ischemic heart disease, n (%) 92 (42) 37 (50.7) 0.196
Congestive heart failure, n (%) 53 (24.4) 23 (31.5) 0.226
Chronic kidney disease, n (%) 32 (14.6) 27 (37) <0.001
Cerebral vascular stroke, n (%) 32 (14.7) 19 (26) 0.027
Hypertension, n (%) 160 (73) 65 (89) 0.005
Dyslipidemia, n (%) 119 (54.6) 55 3(75.) 0.002
Peripheral vascular disease, n (%) 15 (7) 17 (24) <0.001
Osteoarthritis, n (%) 15 (6.9) 11 (15) 0.034
Hypoglycemia, n (%) 10 (4.6) 2 (2.7) 0.492
Diabetes ketoacidosis, n (%) 30 (13.8) 1 (1.4) 0.003
Diabetes complications, n (%)
Retinopathy 28 (12.8) 16 (21.9) 0.061
Foot ulcer 15 (6.9) 13 (17.8) 0.006
Gangrene 3 (1.4) 7 (9.6) 0.001
Lower limb ischemia 7 (3.2) 10 (13.7) 0.001
Abbreviations: DPN, diabetes peripheral neuropathy; IQR, interquartile range.
Table 3 Univariate and Multivariate Conditional Logistic Regression for Risk Factors Associated with DPN
Factor Univariate Analysis Multivariate Analysis
OR (95% CI) p-value OR (95% CI) p-value
Age 1.03 (1.01–1.05) <0.001 1.02 (1.01–1.04) 0.031
Chronic kidney disease
Yes 3.43 (1.87–6.28) <0.001 2.39 (1.23–4.64) 0.010
No 1 1
Cerebral vascular stroke
Yes 2.05 (1.08–3.89) 0.029 1.64 (0.80–3.33) 0.176
No 1 1
Peripheral vascular disease
Yes 4.11 (1.93–8.74) <0.001 3.14 (1.39–7.13) 0.006
No 1 1
Hypertension
Yes 3.00 (1.36–6.62) 0.007 083 (0.27–2.54) 0.740
No 1 1
Dyslipidemia
Yes 2.54 (1.40–4.61) 0.002 1.56 (0.78–313) 0.181
No 1 1
Abbreviations: CI, condence interval; OR, odds ratio.
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(range): 7.9 (1.4–27.7) vs 6.5 (1.5–22.0)], were signi-
cantly higher in South Asians than Europeans.
33,34
As mentioned earlier DPN is believed to be a conse-
quence of the diabetes longstanding hyperglycemia which
is critical for peripheral nerve damage and distal-predomi-
nant nerve ber degeneration.
911
The hyperglycemia of
the chronic diabetes process is compounded by numerous
metabolic aberrations and diabetic microvascular compli-
cations resulting from the disturbed nutritional support
especially of the most distal parts of very long nerve
axons originating in the spinal cord and travel long dis-
tances to supply the lower limbs and the feet in particular.
Additionally, the sparse vascular supply in this area result-
ing from diabetes is likely to cause further hypoxic nerve
damage. Other confounding metabolic aberrations result-
ing from the chronic hypoglycemia include excessive
release of cytokines, and exaggerated oxidative stress.
This topic has been reviewed in detail elsewhere.
9
It is also becoming clear that the duration of diabetes
and glycemic control are the most signicant risk factors
for DPN.
35
In regard to the benet of blood glucose con-
trol, there are reports indicating that aggressive blood
glucose control was associated with lower prevalence of
DPN.
3639
In support of this notion, in the current study,
we found an association between DPN and blood glucose
control as reected by the fasting blood glucose level,
HbA1c and the type of treatment. Therefore, like others
40
the most effective approach to reduce the progression to
neuropathy is aggressive treatment of diabetes hypergly-
cemia towards normoglycemia.
Our nding that multiple risk factors are associated
with the development of DPN in diabetic patients should
direct the attention towards the link between these risk
factors and the increase in diabetes-related complications,
morbidity as well as mortality.
40,41
It was also clear that
age is a signicant risk factor that predisposes to DPN and
this nding was observed by others.
1,2022
In the present
study the vast majority of patients with DPN were type 2
diabetes (90.4%). Similarly, Kästenbauer et al,
23
showed a
higher percentage (16% vs 37.5%) of type 2 diabetic
patients with symptoms of neuropathy compared with
type 1 diabetic patients.
23
Other risk factors including
BMI, number of comorbid diseases such as chronic kidney
disease, hypertension, dyslipidemia, cerebral vascular
stroke, peripheral vascular disease and diabetic ketoacido-
sis were also found to be signicantly associated with
DPN. The close association between DPN and modiable
cardiovascular risk factors (cardiometabolic disease)
including elevated triglyceride levels (hyperlipidemia),
body mass index (BMI), smoking, hypertension and car-
diovascular disease was documented repeatedly in pre-
vious studies.
1,20,21,24,42
However, no specic
mechanisms linking DPN with cardiovascular disease
have been suggested in any of these studies.
It also worth adding that the ndings of the present study
are consistent with those reported from the neighboring Gulf
state of Bahrain. The Bahraini study
22
found that older age,
poor glycemic control, longer duration of diabetes, elevated
cholesterol levels, current smoking, obesity, large waist cir-
cumference, elevated triglycerides levels and hypertension
but not gender were signicant risk factors for DPN.
However, the vast majority of the DPN patients in the
study were females and were on insulin therapy. In contrast,
there were no signicant differences in gender distribution
or treatment modalities when compared to controls. On the
other hand, many other studies have reported a signicant
association between female gender and the prevalence of
DPN.
1,20,21,24
In the multivariate model, we identied three risk
factors that independently correlate with the presence of
DPN. These were age, chronic kidney disease and periph-
eral vascular disease. These risk factors were closely asso-
ciated with DPN and this association has been reported
before.
1,24,26,3743
However, we did not nd any correlation between
smoking and DPN.
24,26,44
Nonetheless, the following dis-
eases were found to be associated with DPN: PVD, kidney
disease, hypertension, dyslipidemia, foot ulcer and ampu-
tation, which is in line with many earlier
studies.
15,37,39,44,45
Our ndings concur with those reported in recent pub-
lished studies on the factors associated with DPN. These
studies were noticeable multi-center studies of long-term
follow-up of 20–25 years.
46,47
Most of these studies con-
rmed that old age, longer diabetes duration, and elevated
HbA1c were the commonest risk factors for the develop-
ment of DPN.
4548
We acknowledge several limitations in our study. The
nature of study design as a retrospective study limits the
accurate assessment of the association between DPN and
risk factors. Therefore, prospective studies are needed to
fully characterize the sequel of DPN in diabetes patients.
Poor documentation of DPN diagnosis and supportive
laboratories investigations (nerve conduction studies and
electromyography) reduced our ability to access important
data needed for the study and to conrm how DPN
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diagnosis was made. Therefore, it is likely that some DPN
patients were missed.
Conclusion
This study identied several risk factors that contributed to
the development of DPN in Saudis. These must be con-
sidered in strategies and campaigns aimed at risk reduction
of cardiovascular and chronic diseases, and consequently
progression of DPN.
Ethics
The study was approved by the Institutional Review
Board, King Abdullah International Medical Research
Centre, King Saud bin Abdulaziz University for Health
Sciences, National Guard Health Affairs. All patient data
accessed complied with relevant data protection and priv-
acy regulations. All procedures performed in the study
involving human participants were in accordance with
the ethical standards of the institutional and/or national
research committee and with the 1964 Helsinki declaration
and its later amendments or comparable ethical standards.
Acknowledgments
We would like to acknowledge the help of the Health
Informatics Department, KAMC.
Author Contributions
All authors made substantial contributions to conception
and design, acquisition of data, or analysis and interpreta-
tion of data; took part in drafting the article or revising it
critically for important intellectual content; agreed to sub-
mit to the current journal; gave nal approval of the
version to be published; and agree to be accountable for
all aspects of the work.
Funding
There is no funding to report.
Disclosure
The authors report no conicts of interest for this work.
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Background: Diabetes mellitus (DM) is a global health care problem that can impose a substantial economic burden. Diabetic peripheral neuropathy (DPN) is a common microvascular complication of DM that increases the potential for morbidity and disability due to ulceration and amputation. Though there is a significant amount of variation in the primary studies on DM regarding the prevalence of DPN in Africa. Hence, this study was aimed to estimate the overall prevalence of DPN in DM patients in Africa. Methods: PubMed, Scopus, Google Scholar, African Journals OnLine, WHO African Library, and the Cochrane Review were systematically searched online to retrieve related articles. The Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines was followed. Heterogeneity across the included studies was evaluated by the inconsistency index (I2). Publication bias was examined by funnel plot and Egger's regression test. The random-effect model was fitted to estimate the pooled prevalence of diabetic peripheral neuropathy among patients in Africa. The meta-analysis was performed using the STATA™ Version 14 software. Results: Twenty-three studies which includes 269,691 participants were included in the meta-analysis. The overall pooled prevalence of diabetic peripheral neuropathy was 46% (95% CI:36.21-55.78%). Based on the subgroup analysis, the highest prevalence of diabetic peripheral neuropathy in DM patients was reported in West Africa at 49.4% (95% CI: 32.74, 66.06). Conclusion: This study revealed that the overall prevalence of diabetic peripheral neuropathy is relatively high in Africa. Hence, DPN needs situation-based interventions and preventive strategies, which are specific to the country. Further meta-analysis is needed to identify associated factors for the occurrence of diabetic peripheral neuropathy.
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Background: Diabetic peripheral neuropathy (DPN) is one of the most common complications of diabetes and is responsible for morbidity and disability among diabetic patients. Objectives: The aim of this study was to assess the prevalence of painful DPN and its associated risk factors in patients with diabetes mellitus. Materials and Methods: A cross‑sectional study was conducted among 430 diabetic patients attending primary healthcare centres (PHC) in AL Madinah city, Saudi Arabia. The validated Douleur Neuropathique‑4 (DN4) questionnaire was used to identify the presence of painful DPN. Results: The majority were female (54.7%) and had type 2 diabetes mellitus (74.9%). The prevalence of DPN was 30.1% in type 2 diabetic patients and 25.9% in type 1 diabetic patients with an overall prevalence of 29.1%. DPN was associated significantly with age, duration of diabetes milieus, uncontrolled A1c, and positive family history of diabetes mellitus (P < 0.05). All the investigated comorbidities were also associated significantly with DPN (P < 0.05). Conclusions: The prevalence of DPN was 25.9% and was associated with age duration of DM and uncontrolled HbA1c. PHC physicians treating diabetes should be more aware of the importance of screening for DPN and the treatment plan
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Diabetic peripheral neuropathy (DPN) is a common chronic complication of diabetes mellitus. It leads to distressing and expensive clinical sequelae such as foot ulceration, leg amputation, and neuropathic pain (painful-DPN). Unfortunately, DPN is often diagnosed late when irreversible nerve injury has occurred and its first presentation may be with a diabetic foot ulcer. Several novel diagnostic techniques are available which may supplement clinical assessment and aid the early detection of DPN. Moreover, treatments for DPN and painful-DPN are limited. Only tight glucose control in type 1 diabetes has robust evidence in reducing the risk of developing DPN. However, neither glucose control nor pathogenetic treatments are effective in painful-DPN and symptomatic treatments are often inadequate. It has recently been hypothesized that using various patient characteristics it may be possible to stratify individuals and assign them targeted therapies to produce better pain relief. We review the diagnostic techniques which may aid the early detection of DPN in the clinical and research environment, and recent advances in precision medicine techniques for the treatment of painful-DPN.
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Purpose of Review Diabetic peripheral neuropathy eventually affects nearly 50% of adults with diabetes during their lifetime and is associated with substantial morbidity including pain, foot ulcers, and lower limb amputation. This review summarizes the epidemiology, risk factors, and management of diabetic peripheral neuropathy and related lower extremity complications. Recent Findings The prevalence of peripheral neuropathy is estimated to be between 6 and 51% among adults with diabetes depending on age, duration of diabetes, glucose control, and type 1 versus type 2 diabetes. The clinical manifestations are variable, ranging from asymptomatic to painful neuropathic symptoms. Because of the risk of foot ulcer (25%) and amputation associated with diabetic peripheral neuropathy, aggressive screening and treatment in the form of glycemic control, regular foot exams, and pain management are important. There is an emerging focus on lifestyle interventions including weight loss and physical activity as well. Summary The American Diabetes Association has issued multiple recommendation statements pertaining to diabetic neuropathies and the care of the diabetic foot. Given that approximately 50% of adults with diabetes will be affected by peripheral neuropathy in their lifetime, more diligent screening and management are important to reduce the complications and health care burden associated with the disease.
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Background: Lower extremity amputation (LEA) is a potential sequelae of diabetic foot ulceration (DFU) and is associated with huge morbidly and mortality. Low and middle income countries are currently at the greatest risk of diabetes-related complications and deaths. We sought to identify demographic, clinical and laboratory variables that significantly predict LEA in patients hospitalized for DFU. Methods: The Multi-center Evaluation of Diabetic Foot Ulcer in Nigeria (MEDFUN) was an observational study conducted between March 2016 and April 2017 in six tertiary healthcare institutions. We prospectively followed 336 diabetic patients hospitalized for DFU and managed by a multidisciplinary team until discharge or death. Demographic and diabetes-related information and ulcer characteristics were documented. Patients were evaluated for neuropathy, peripheral arterial disease (PAD) and medical co-morbidities while relevant laboratory and imaging tests were performed. The study end-points were ulcer healing, LEA, duration of hospitalization and mortality. Here we present data on amputation. Results: One hundred and nineteen subjects (35.4%) underwent LEA during the follow-up period. Univariate predictors of LEA were ulcer duration more than 1 month prior to hospitalization (P < 0.001), PAD (P < 0.001), Wagner grade ≥ 4 (P < 0.001), wound infection (P 0.041), Proteinuria (P 0.021), leucocytosis (P 0.001) and osteomyelitis (P < 0.001). On multivariate regression, only three variables emerged as significant independent predictors of LEA and these include: ulcer duration more than 1 month (O.R. 10.3, 95% C.I. 4.055-26.132), PAD (O.R. 2.8, 95% C.I. 1.520-5.110) and presence of osteomyelitis (O.R. 5.6, 95% C.I. 2.930-10.776). Age, gender, diabetes type and duration, neuropathy, glycemic control and anemia did not predict LEA in the studied population. Conclusion: We identified duration of ulcer greater than 1 month, PAD, Wagner grade 4 or higher, proteinuria, leucocytosis, wound infection and osteomyelitis as the significant predictors of LEA in patients hospitalized for DFU. Prompt attention to these risk factors may reduce amputation rate among these patients.
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Objective: Diabetic peripheral neuropathy (DPN) is a common microvascular complication of diabetes mellitus (DM) and may progress to diabetic foot, which frequently leads to amputation and/or disability and death. Data is scanty on the burden of diabetic peripheral neuropathy in Tanzania. The aim of this study was to assess the burden of peripheral neuropathy, its severity, and the associated factors. Methods: The study was a cross-sectional hospital-based study and was carried out from October 2017 to March 2018 among adolescent and adult patients attending Kilimanjaro Christian Medical Center (KCMC) diabetes clinic. Results: A total of 327 diabetic patients, females n=215 (65.7%) and males n=121 (34.3%), were included in the study. The mean age was 57.2 yrs. A total of 238 (72%) had type 2 and 89 (27.2%) had type1 DM. The prevalence of peripheral neuropathy was 72.2% of whom 55% were severe, 19% were moderate, and 26% were mild. The severity of neuropathy increased with the increase in age >40 years (p < 0.001) and increase in body mass index (p<0.001) and duration of diabetes; duration >7 years (p <0.006). The main associated factors were age >40 years, OR 2.8 (1.0-7.7), >60 years, OR 6.4 (2.3-18.2), obesity, OR 6.7 (0.9-27.7), and hypertension, OR 4.3 (2.2-8.2). Conclusion: More than half of the patients included in this study were found to have neuropathy, nearly half of whom presented with the severe form. The main risk factors were increasing age, increasing duration of diabetes, obesity, and hypertension. Diabetic peripheral neuropathy is underdiagnosed in northern Tanzania where screening for neuropathy is not routinely done.
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Diabetic peripheral neuropathy (DPN) is the most common complication of diabetes, and its progression significantly worsens the patient's quality of life. This study investigated the prevalence and risk factors associated with DPN in a large sample of Beijing individuals with type 1 and 2 diabetes, as well as compared the diagnostic methods for DPN. A total of 2,048 diabetic patients from 13 centers in Beijing were assessed for DPN through questionnaires and examination. Patients were divided into DPN group and suspected DPN/non-DPN group. The demographic, clinical and biological characteristics between the two groups were compared. Binary logistic regression analysis was performed to identify potential variables associated with DPN in diabetic patients. The diagnostic methods for DPN were also compared. Among the 2,048 diabetic patients, 73 cases of type 1 diabetes mellitus, 1,975 cases of type 2 diabetes were included in this study. Among them, 714 (34.86%) were identified with DPN, 537 (26.22%) were suspected of having DPN, and 797 (38.92%) were identified without DPN. Patient's age, duration of diabetes, and diabetic retinopathy were the significant independent risk factor for DPN among patients with type 2 diabetes. The odds ratio (OR) was 1.439 (95% confidence interval (CI): 1.282–1.616, P < 0.001), 1.297 (95% CI: 1.151–1.462, P < 0.001), and 0.637 (95% CI: 0.506–0.802, P < 0.001), respectively. Ankle reflex, temperature sensation plus vibration sensation are the best screening test for patients with type 1 and 2 diabetes. The Youden indexes were 62.2 and 69.8%, respectively. The prevalence rates of DPN in the Chinese patients with type 1 and type 2 diabetes in Beijing were 21.92 and 35.34%, respectively. Patient's age, duration of diabetes, and diabetic retinopathy are the independent risk factors for DPN.
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Background Low foot ulcer risk in South Asian, compared with European, people with type 2 diabetes in the UK has been attributed to their lower levels of neuropathy. We have undertaken a detailed study of corneal nerve morphology and neuropathy risk factors, to establish the basis of preserved small nerve fibre function in South Asians versus Europeans. Methods In a cross‐sectional, population‐based study, age‐ and sex‐matched South Asians (n=77) and Europeans (n=78) with type 2 diabetes underwent neuropathy assessment using corneal confocal microscopy, symptoms, signs, quantitative sensory testing, electrophysiology and autonomic function testing. Multivariable linear regression analyses determined factors accounting for ethnic differences in small fibre damage. Results Corneal nerve fibre length (22.0±7.9 vs. 19.3±6.3 mm/mm²; P=0.037), corneal nerve branch density (geometric mean (range): 60.0 (4.7‐246.2) vs. 46.0 (3.1‐129.2) no./mm²; P=0.021) and heart rate variability (geometric mean (range): 7.9 (1.4‐27.7) vs. 6.5 (1.5‐22.0); P=0.044), were significantly higher in South Asians vs. Europeans. All other neuropathy measures did not differ, except for better sural nerve amplitude in South Asians (geometric mean (range): 10.0 (1.3‐43.0) vs. 7.2 (1.0‐30.0); P=0.006). Variables with the greatest impact on attenuating the P value for age‐ and HbA1C‐adjusted ethnic difference in corneal nerve fibre length (P=0.032) were pack‐years smoked (P=0.13), BMI (P=0.062) and triglyceride levels (P=0.062). Conclusions South Asians have better preserved small nerve fibre integrity than equivalent Europeans; furthermore, classic, modifiable risk factors for coronary heart disease are the main contributors to these ethnic differences. We suggest that improved autonomic neurogenic control of cutaneous blood flow in Asians may contribute to their protection against foot ulcers.
Article
The DCCT/EDIC study demonstrated that intensive glucose control reduced the risk of developing diabetic peripheral neuropathy (DPN) and cardiovascular autonomic neuropathy (CAN). We evaluated multiple risk factors and phenotypes associated with DPN and CAN in this large, well-characterized cohort of participants with type 1 diabetes, followed for >23 years. DPN was defined by symptoms, signs, and nerve conduction study abnormalities in ≥2 nerves; CAN was assessed using standardized cardiovascular reflex tests. Generalized estimating equation models assessed the association of DPN and CAN with individual risk factors measured repeatedly. During DCCT/EDIC, 33% of participants developed DPN and 44% CAN. Higher mean HbA1c was the most significant risk factor for DPN, followed by longer duration, older age, greater height, macroalbuminuria, higher mean pulse rate, β-blocker use, and sustained albuminuria. The most significant risk factor for CAN was older age, followed by longer duration, higher mean HbA1c, sustained albuminuria, higher mean and most recent pulse rate, higher mean systolic blood pressure, β-blocker use, eGFR<60 mL/min/1.73m2, and current cigarette smoking. These findings identify risk factors and phenotypes of participants with diabetic neuropathy that can be used in the design of new interventional trials and for personalized approaches to neuropathy prevention.