Reduced incidence of lower-extremity amputations in a Danish diabetes population from 2000 to 2011

Abstract

Diabetic foot disease and amputations severely reduce quality of life and have major economic consequences. The aim of this study was to estimate time trends in the incidence of lower-extremity amputations in Danish people with diabetes.
We studied major and minor lower-extremity amputations from 2000 to 2011 among 11 332 people with diabetes from the Steno Diabetes Center. Amputations were identified by linkage of the electronic medical system with the National Patient Registry. Sex-specific incidence rates of amputations by age, diabetes duration, calendar time and diabetes type were modelled by Poisson regression.
From 2000 to 2011, 384 incident lower-extremity amputations (205 major, 179 minor) occurred during 100 495 years of patient follow-up. From 2000 to 2011, the incidence of all lower-extremity amputations decreased by 87.5% among men and 47.4% among women with Type 1 diabetes and by 83.3% among men and 79.1% among women with Type 2 diabetes (P < 0.001). In particular, there was a decline in major lower-extremity amputations. In 2011, the incidence rates of major lower-extremity amputations were 0.25 (95% CI 0.07-0.82) among men and 0.21 (95% CI 0.06-0.71) among women per 1000 patient-years at age 50 years and 0.56 (95% CI 0.18-1.89) among men and 0.41 (95% CI 0.16-1.09) among women per 1000 patient-years at age 70 years. No significant change in incidence of minor amputations was observed.
The incidence of major lower-extremity amputations reduced significantly from 2000 to 2011 in Danish people with diabetes followed at a diabetes specialist centre. This article is protected by copyright. All rights reserved.

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Short Report: Complications
Reduced incidence of lower-extremity amputations in a
Danish diabetes population from 2000 to 2011
M. E. Jørgensen, T. P. Almdal and K. Færch
Steno Diabetes Center, Gentofte, Denmark
Accepted 18 September 2013
Abstract
Aims Diabetic foot disease and amputations severely reduce quality of life and have major economic consequences. The
aim of this study was to estimate time trends in the incidence of lower-extremity amputations in Danish people with
diabetes.
Methods We studied major and minor lower-extremity amputations from 2000 to 2011 among 11 332 people with
diabetes from the Steno Diabetes Center. Amputations were identified by linkage of the electronic medical system with
the National Patient Registry. Sex-specific incidence rates of amputations by age, diabetes duration, calendar time and
diabetes type were modelled by Poisson regression.
Results From 2000 to 2011, 384 incident lower-extremity amputations (205 major, 179 minor) occurred during
100 495 years of patient follow-up. From 2000 to 2011, the incidence of all lower-extremity amputations decreased by
87.5% among men and 47.4% among women with Type 1 diabetes and by 83.3% among men and 79.1% among
women with Type 2 diabetes (P<0.001). In particular, there was a decline in major lower-extremity amputations. In
2011, the incidence rates of major lower-extremity amputations were 0.25 (95% CI 0.07–0.82) among men and 0.21
(95% CI 0.06–0.71) among women per 1000 patient-years at age 50 years and 0.56 (95% CI 0.18–1.89) among men
and 0.41 (95% CI 0.16–1.09) among women per 1000 patient-years at age 70 years. No significant change in incidence
of minor amputations was observed.
Conclusion The incidence of major lower-extremity amputations reduced significantly from 2000 to 2011 in Danish
people with diabetes followed at a diabetes specialist centre.
Diabet. Med. 00, 000–000 (2013)
Introduction
Diabetes is associated with severe complications, including
foot disease and resulting amputations [1]. Diabetic foot
disease and amputations severely reduce the quality of life
and have major economic consequences for patients, their
families and society. In the 1990s, the healthcare service in
Denmark and many other countries was reorganized, with
the establishment of specialized vascular clinics, multidisci-
plinary centralized diabetic foot clinics and ultrasound
screening surveillance programmes [2]. In Denmark, these
changes were paralleled by a decrease in major
lower-extremity amputations as well as an increase in the
number of revascularization procedures in both people with
and without diabetes [2]. Data from other countries also
support a reduction in the incidence of lower-extremity
amputations after introduction of specialist diabetic foot
clinics [3]. A recent report from Scotland based on a
nationwide diabetes register reported that the overall reduc-
tion in incidence of lower-extremity amputations observed
over a 5-year period (2004–2008) was mainly caused by a
reduction in the incidence of major amputations [4].
In the present study we examined changes in the incidence
of major and minor lower-extremity amputations among
men and women with Type 1 diabetes and Type 2 diabetes
followed at a Danish adult diabetes specialist centre during
the period 2000–2011.
Research design and methods
All people with diabetes recorded in the electronic medical
record system at the Steno Diabetes Center during the period
from 1 January 2000 to 31 December 2011 were included in
this open cohort (n=11 427). People without date of
Correspondence to: Marit Eika Jørgensen. E-mail: MAEJ@steno.dk
ª2013 The Authors.
Diabetic Medicine ª2013 Diabetes UK 1
DIABETICMedicine
DOI: 10.1111/dme.12320

diabetes diagnosis and other inconsistencies in registration
were excluded, leaving 11 332 people for analysis (Type 1
diabetes: n=5116, Type 2 diabetes: n=6216). Thus, for all
people in the analysis, we had recordings of date of birth,
date of diabetes diagnosis, presence of complications, and
date and type of lower-extremity amputation (classified as
major or minor in this analysis). The diabetes data were
linked to the National Patient Register using the unique
personal identification number for all persons in Denmark.
The National Patient Register was established in 1977,
contains electronic records of all patient discharges from
hospitals and, since 1994, also contains records of all
treatments in outpatient clinics. Each contact is recorded
with one or more diagnosis codes in the International
Classification of Diseases (ICD)-10 (ICD-8 before 1999).
Coverage was 100% as reporting is compulsory. A
lower-extremity amputation was defined as a complete loss
in the transverse anatomical plane of any part of the limb.
Major amputation was any through or proximal to the ankle
(ICD-10, Z89.5–Z89.7), and minor amputations distal to the
ankle (ICD-10, Z89.4).
People with diabetes were followed from 1 January 2000 or,
after that day, from entry date to the Steno Diabetes Center
until the first amputation, death or the last update of the
electronic medical record with the Central Person Register
system (31 December 2011). The follow-up (risk time) of the
population was split into 3-month intervals, each interval
recording the current age, date and diabetes duration.
Incidence rates of lower-extremity amputations were
analysed by a Poisson model, using log–person–time, sepa-
rately for each sex and diabetes type. The rates were analysed
with smooth terms of current age, date of follow-up and
duration of diabetes, with a simple one-parameter (product)
interaction between age and diabetes duration [5]. The
midpoints of age, period and duration categories were used
as continuous covariates, and the effect of these were taken
as smooth parametric functions, implemented as natural
splines. Amputation incidence rates were modelled by age,
calendar time and diabetes duration. All analyses were
performed separately for men and women and for Type 1
diabetes and Type 2 diabetes. Data are reported with 95%
confidence intervals. All analyses and graphs were generated
with R (‘R’ 3.0.1, Vienna, Austria).
Results
The median (interquartile range) age of the cohort at baseline
was 44 (32–57) and 60 (51–75) years for Type 1 diabetes
and Type 2 diabetes, with a median (interquartile range)
diabetes duration of 19 (8–29) and 9 (4–14) years, respec-
tively. Fifty-six per cent of people with Type 1 diabetes and
28% of people with Type 2 diabetes in the cohort had
retinopathy at study entry, while 35% of both diabetes types
had neuropathy. Cardiovascular disease was present in 35%
of people with Type 1 diabetes and 60% of people with
Type 2 diabetes, and 25 and 23%, respectively, were
diagnosed with nephropathy.
In the period 2000–2011 a total of 384 incident
lower-extremity amputations (205 major, 179 minor)
occurred in the population during 100 495 patient-years of
follow-up.
Amputation rates by diabetes type, age, sex, diabetes
duration and calendar time are shown in Fig. 1a–f. Incidence
rates were not significantly different in Type 1 diabetes and
Type 2 diabetes. Among people with Type 2 diabetes,
amputation rates were higher among men compared with
women (Fig. 1a–b). From 2000–2011, the incidence of all
lower-extremity amputations decreased by 87.5% among
men and 47.4% among women with Type 1 diabetes and by
83.3% among men and 79.1% among women with Type 2
diabetes (Fig. 1c–d). In particular, there was a decline in
major lower-extremity amputations. In 2011, the incidence
rates of major lower-extremity amputations were 0.25
(95% CI 0.07–0.82) among men and 0.21 (95% CI
0.06–0.71) among women per 1000 patient-years at age
50 years and 0.56 (95% CI 0.18–1.89) among men and 0.41
(95% CI 0.16–1.09) among women per 1000 patient-years
at age 70 years. This corresponded to a decrease in incidence
from 2000–2011 of 90.9% among men and 81.8% among
women with Type 1 diabetes and 94.7% among men and
85.1% among women with Type 2 diabetes (P<0.001). No
significant change in incidence of minor lower-extremity
amputations was observed.
Amputation rates increased with increasing diabetes dura-
tion (Fig. 1e–f), were strongest among men and with the
steepest increase during the first 20 years in Type 1 diabetes.
Discussion
In a Danish population of people with diabetes followed at
a diabetes specialist centre, the rate of lower-extremity
What’s new?
•Using register linkage, this study reports 11-year trends
in amputation rates among men and women with
Type 1 and Type 2 diabetes in Denmark.
What this study adds:
•Updated information about trends in major and minor
amputations in a large population of people with
Type 1 and Type 2 diabetes.
•Incidence rates of lower-extremity amputations have
decreased by more than 80% during the last decade.
•The decline in lower-extremity amputations is particu-
larly a result of a decline in the incidence of major
amputations.
2
ª2013 The Authors.
Diabetic Medicine ª2013 Diabetes UK
DIABETICMedicine Time trends in amputations M. E. Jørgensen et al.

amputations decreased substantially from 2000 to 2011.
Absolute amputation rates until 2008 were similar to other
studies [4,6–9]. However, to our knowledge, no information
on amputation rates in diabetes with follow-up after 2008
has been published. The current study provides the most
recent data on time trends in lower-extremity amputations,
with information available until the end of 2011. An
encouraging finding is that amputation rates have decreased
further since 2008, particularly for major amputations.
These results are consistent with recent observations in
Scotland, showing a 41% reduction in the incidence of
lower-extremity amputations from 2004 to 2008 [4]. Tem-
poral trends in lower-extremity amputations were also
studied in 2 730 742 older American people with peripheral
artery disease using Medicare claims data [10]. A reduction
in the incidence of amputations from 7258 per 100 000
patients in 2000 to 5790 per 100 000 patients in 2008 was
found. Diagnosis of diabetes was one of the most important
0
1
2
3
4
5
Age (years)
Amputations 2011
(/1000 patient-years)
Type 1
0
1
2
3
4
5
Age (years)
Amputations 2011
(/1000 patient-years)
Type 2
0.2
0.5
1.0
2.0
5.0
10.0
20.0
Date of follow−up
Amputations (rate ratio)
Type 1
0.2
0.5
1.0
2.0
5.0
10.0
20.0
Date of follow−up
Amputations (rate ratio)
Type 2
40 50 60 70 80 90 40 50 60 70 80 90
2000 2002 2004 2006 2008 2010 2012 2000 2002 2004 2006 2008 2010 2012
010 20 30 40 010 20 30 40
0.2
0.5
1.0
2.0
5.0
10.0
20.0
Diabetes duration (years)
Amputations (rate ratio)
Type 2
0.2
0.5
1.0
2.0
5.0
10.0
20.0
Diabetes duration (
y
ears)
Amputations (rate ratio)
Type 1
(a) (b)
(c) (d)
(e) (f)
FIGURE 1 All lower-extremity amputations/1000 person years (95% CI) according to age in Type 1 diabetes (a) and Type 2 diabetes (b). Rate ratios
by calendar time in Type 1 diabetes (c) and Type 2 diabetes (d), and rate ratios by diabetes duration in Type 1 diabetes (e) and Type 2 diabetes (f).
Age-specific amputation rates are for 1 January 2011 for 10 years of diabetes duration. Bold lines are means; thin lines are 95% confidence limits.
Red curves are for women; blue curves are for men.
ª2013 The Authors.
Diabetic Medicine ª2013 Diabetes UK 3
Research article DIABETICMedicine

factors associated with lower-extremity amputations (odds
ratio 2.40, 95% CI 2.38–2.43) [10].
Important improvements in metabolic risk factors and
lifestyle factors such as smoking [2], in combination with
increased emphasis on early and aggressive treatment of foot
ulcers and better patient education, are likely to explain the
observed reduction in lower-extremity amputations over the
last decade. While the incidence of major amputations in
particular has decreased, no change was observed in the
incidence of minor amputations. This finding was not
surprising as minor amputations are often undertaken in an
attempt to avoid major amputations [11,12]. However, in an
American study of the general population, both the incidence
of major and minor amputations decreased from 2000 to
2004 [8], underscoring the large variability in recorded
amputation rates between countries [3]. Overall, our results
indicate that establishment of specialized multidisciplinary
diabetic clinics, screening for complications and performance
of prophylactic vascular surgery is beneficial, especially in
terms of preventing major lower-extremity amputations.
There are several challenges when estimating time trends
in diabetes-related morbidity and mortality. Data from most
studies of diabetes-related lower-extremity amputations have
been obtained from cross-sectional unlinked studies. Such
data from cross-sectional studies are more susceptible to
numerator–denominator biases. The number of people with
diabetes used as denominator may be biased because of
changes in the way cases of diabetes are diagnosed, registered
or treated. Because our population with diabetes is not
drawn from a register, but from the patient pool at the Steno
Diabetes Center, it is unlikely that the observed reduction in
amputations is related to an improvement in the registration
of people with diabetes. Moreover, our study is unaffected by
the recent shift in diagnostic criteria [13], because none of the
patients followed were diagnosed with diabetes after 2011.
Furthermore, a major strength of this study is the detailed
information on diabetes type, diabetes duration and the
precise estimate of amputations.
On the one hand, the population with Type 1 diabetes at
the Steno Diabetes Centre constitutes a representative
subsample of the total Danish population with Type 1
diabetes and the findings in this study therefore may reflect
a general trend in people with Type 1 diabetes. On the other
hand, the majority of people with Type 2 diabetes in
Denmark are treated in general practice and only compli-
cated cases are referred to treatment in hospital outpatient
clinics. The population with Type 2 diabetes followed in this
study is therefore highly selective and the results may only
apply to the most complicated cases of Type 2 diabetes.
Criteria for referral of patients with Type 2 diabetes to the
Steno Diabetes Centre include severe hyperglycaemia or
progressive diabetes complications. As these criteria were
more or less unchanged during the study follow-up, it is
unlikely that the decrease in amputations is primarily
explained by improvements in health for people with Type 2
diabetes. However, the extent to which the decline in risk of
amputations is attributable to treatment or lifestyle factors is
not possible to determine because this information was not
available.
In conclusion, the present study reveals in a Danish
population of both Type 1 diabetes and Type 2 diabetes
(1) that incidence rates of lower-extremity amputations have
decreased during the last decade and (2) that this is
particularly a result of a decline in incidence of major
amputations.
Funding sources
None.
Competing interests
MEJ and KF are employed by the Steno Diabetes Center A/S,
a research hospital working in the Danish National Health
Service and owned by Novo Nordisk A/S. The Steno
Diabetes Center receives part of its core funding from
unrestricted grants from the Novo Foundation and Novo
Nordisk A/S. MEJ, KF and TPA own shares in Novo Nordisk
A/S.
Acknowledgments
We would like to thank Annemette Anker Nielsen, Steno
Diabetes Center A/S who entered all patient data.
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