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A healthy lifestyle mitigates the risk of heart disease related to type 2 diabetes: a prospective nested case–control study in a nationwide Swedish twin cohort

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Aims/hypothesis We aimed to examine the association between type 2 diabetes and major subtypes of heart disease, to assess the role of genetic and early-life familial environmental factors in this association and to explore whether and to what extent a healthy lifestyle mitigates the risk of heart disease related to type 2 diabetes. Methods In this prospective nested case–control study based on the Swedish Twin Registry, 41,463 twin individuals who were aged ≥40 and heart disease-free were followed up for 16 years (from 1998 to 2014) to detect incident heart disease. Type 2 diabetes was ascertained from self-report, the National Patient Registry and glucose-lowering medication use. Heart disease diagnosis (including coronary heart disease, cardiac arrhythmias and heart failure) and onset age were identified from the National Patient Registry. Healthy lifestyle-related factors consisted of being a non-smoker, no/mild alcohol consumption, regular physical activity and being non-overweight. Participants were divided into three groups according to the number of lifestyle-related factors: (1) unfavourable (participants who had no or only one healthy lifestyle factor); (2) intermediate (any two or three); and (3) favourable (four). Generalised estimating equation models for unmatched case–control design and conditional logistic regression for co-twin control design were used in data analyses. Results Of all participants, 2304 (5.5%) had type 2 diabetes at baseline. During the observation period, 9262 (22.3%) had any incident heart disease. In unmatched case–control analyses and co-twin control analyses, the multi-adjusted OR and 95% CI of heart disease related to type 2 diabetes was 4.36 (3.95, 4.81) and 4.89 (3.88, 6.16), respectively. The difference in ORs from unmatched case–control analyses vs co-twin control analyses was statistically significant (OR 1.57; 95% CI 1.42, 1.73; p < 0.001). In stratified analyses by type 2 diabetes, compared with an unfavourable lifestyle, an intermediate lifestyle or a favourable lifestyle was associated with a significant 32% (OR 0.68; 95% CI 0.49, 0.93) or 56% (OR 0.44; 95% CI 0.30, 0.63) decrease in heart disease risk among patients with type 2 diabetes, respectively. There were significant additive and multiplicative interactions between lifestyle and type 2 diabetes on heart disease. Conclusions/interpretation Type 2 diabetes is associated with more than fourfold increased risk of heart disease. The association still remains statistically significant, even after fully controlling for genetic and early-life familial environmental factors. However, greater adherence to a healthy lifestyle may significantly mitigate the risk of heart disease related to type 2 diabetes.Graphical abstract
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ARTICLE
A healthy lifestyle mitigates the risk of heart disease related to type 2
diabetes: a prospective nested casecontrol study in a nationwide
Swedish twin cohort
Rongrong Yang
1,2
&Hui Xu
2,3
&Nancy L. Pedersen
4,5
&Xuerui Li
2
&Jing Yu
6
&Cuiping Bao
7
&Xiuying Qi
2
&Weili Xu
2,8
Received: 8 June 2020 /Accepted: 28 September 2020
#The Author(s) 2020
Abstract
Aims/hypothesis We aimed to examine the association between type 2 diabetes and major subtypes of heart disease, to assess the
role of genetic and early-life familial environmental factors in this association and to explore whether and to what extent a healthy
lifestyle mitigates the risk of heart disease related to type 2 diabetes.
Methods In this prospective nested casecontrol study based on the Swedish Twin Registry, 41,463 twin individuals who were
aged 40 and heart disease-free were followed up for 16 years (from 1998 to 2014) to detect incident heart disease. Type 2
diabetes was ascertained from self-report, the National Patient Registry and glucose-lowering medication use. Heart disease
diagnosis (including coronary heart disease, cardiac arrhythmias and heart failure) and onset age were identified from the
National Patient Registry. Healthy lifestyle-related factors consisted of being a non-smoker, no/mild alcohol consumption,
regular physical activity and being non-overweight. Participants were divided into three groups according to the number of
lifestyle-related factors: (1) unfavourable (participants who had no or only one healthy lifestyle factor); (2) intermediate (any two
or three); and (3) favourable (four). Generalised estimating equation models for unmatched casecontrol design and conditional
logistic regression for co-twin control design were used in data analyses.
Results Of all participants, 2304 (5.5%) had type 2 diabetes at baseline. During the observation period, 9262 (22.3%) had any
incident heart disease. In unmatched casecontrol analyses and co-twin control analyses, the multi-adjusted OR and 95% CI of
heart disease related to type 2 diabetes was 4.36 (3.95, 4.81) and 4.89 (3.88, 6.16), respectively. The difference in ORs from
unmatched casecontrol analyses vs co-twin control analyses was statistically significant (OR 1.57; 95% CI 1.42, 1.73;
p< 0.001). In stratified analyses by type 2 diabetes, compared with an unfavourable lifestyle, an intermediate lifestyle or a
favourable lifestyle was associated with a significant 32% (OR 0.68; 95% CI 0.49, 0.93) or 56% (OR 0.44; 95% CI 0.30,
0.63) decrease in heart disease risk among patients with type 2 diabetes, respectively. There were significant additive and
multiplicative interactions between lifestyle and type 2 diabetes on heart disease.
Rongrong Yang and Hui Xu contributed equally to this manuscript.
Supplementary Information The online version contains
supplementary material available at https://doi.org/10.1007/s00125-020-
05324-z.
*Xiuying Qi
qixiuying@tmu.edu.cn
*Weili Xu
weili.xu@ki.se
1
Public Health Science and Engineering College, Tianjin University
of Traditional Chinese Medicine, Tianjin, China
2
Department of Epidemiology and Biostatistics, School of Public
Health, Tianjin Medical University, Tianjin, China
3
Big Data and Engineering Research Center, Beijing Childrens
Hospital, Capital Medical University, National Center for Childrens
Health, Beijing, China
4
Department of Medical Epidemiology and Biostatistics, Karolinska
Institutet, Stockholm, Sweden
5
Department of Psychology, University of Southern California, Los
Angeles, CA, USA
6
Department of Physiology and Pathophysiology, School of Basic
Medicine, Tianjin Medical University, Tianjin, China
7
Department of Radiology, Tianjin Union Medical Centre,
Tianjin, China
8
Aging Research Center, Department of Neurobiology, Health Care
Sciences and Society, Karolinska Institutet and Stockholm
University, Stockholm, Sweden
https://doi.org/10.1007/s00125-020-05324-z
/ Published online: 10 November 2020
Diabetologia (2021) 64:530–539
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
Conclusions/interpretation Type 2 diabetes is associated with more than fourfold increased risk of heart disease. The association
still remains statistically significant, even after fully controlling for genetic and early-life familial environmental factors.
However, greater adherence to a healthy lifestyle may significantly mitigate the risk of heart disease related to type 2 diabetes.
Keywords Heart disease .Lifestyle .Prospectivenestedcasecontrol study in twins .The SwedishTwin Registry .Type 2 diabetes
Abbreviations
AP Attributable proportion
GEE Generalised estimating equation
NPR National Patient Registry
RERI Relative excess risk due to interaction
SALT Screening Across the Lifespan Twin study
SI Synergy index
STR Swedish Twin Registry
Introduction
Worldwide, diabetes affected 451 million people (8.4% of the
worlds population) in 2017, and this number might dramati-
cally rise to 693 million (9.9%) by 2045 [1]. Patients with type
2 diabetes are at increased risk of several chronic diseases and
associated clinical complications, such as heart disease [2],
which, in turn, is associated with cerebral vascular disease,
dementia, disability and premature mortality [3].
Coronary heart disease, heart failure and cardiac arrhyth-
mias are the common types of heart disease [3]. Thus far,
population-based longitudinal studies have consistently
shown that type 2 diabetes is associated with the risk of total
CVD, mainly including coronary heart disease and stroke
[2,47]. However, the associations between type 2 diabetes
and certain subtypes of heart disease independently remain
unclear. Several cohort studies examined the relationship
between type 2 diabetes and atrial fibrillation and flutter, and
showed inconsistent results [812]. Discrepancies in previous
findings can be attributed to the different study populations,
follow-up times and sample size, and lack of consideration of
possible confounders.
Although type 2 diabetes may be linked to heart disease
through several biologically plausible pathways, our under-
standing of the mechanisms for such an association is still
limited. Both type 2 diabetes and heart disease are complex
genetic and lifestyle-related disorders [3]. Genetic and early-
life familial environmental factors may contribute to the
development of type 2 diabetes [13] and heart disease [14].
However, their role in the association between type 2 diabetes
and heart disease is uncertain. Twins are generally reared
together and share genetic background. Thus, twin studies
provide the possibility to assess whether genetic and/or early
familial environmental factors play a role in a given associa-
tion [15]. In addition, previous studies have suggested that an
individual healthy lifestyle factor (such as maintaining a
531Diabetologia (2021) 64:530–539
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normal weight, being a non-smoker, non-heavy drinking or
regular exercise) was associated with lower risk of both type 2
diabetes and CVD in the general population [3,16]. Currently,
accumulating evidence has shown that adopting an overall
and combined healthy lifestyle can be a more effective
prevention strategy for patients with type 2 diabetes to reduce
the risk of cardiovascular complications (such as cause-
specific mortality rate) [17,18]. However, the question
remains whether and to what extent a combined healthy life-
style may counteract the risk of heart disease associated with
type 2 diabetes.
In the current study, we sought to: (1) examine the associ-
ation between type 2 diabetes and the risk of heart disease
including its major subtypes; (2) explore whether genetic
and early-life familial environmental factors play a role in this
association; and (3) investigate whether and to what extent a
healthy lifestyle could mitigate the risk of heart disease related
to type 2 diabetes.
Methods
Study population This prospective, nested casecontrol study
included twins from the nationwide Swedish Twin Registry
(STR), which was started in the 1960s [19]. In 19982002, all
living twins in the registry who were born in 1958 or earlier
were invited to participate in the Screening Across the
Lifespan Twin study (SALT), a full-scale screening that gath-
ered data on an extended set of variables via computer-
assisted telephone interviews. Out of 44,919 twin individuals
eligible for the telephone interview, we excluded 3184 with
heart disease before screening and 272 with type 1 diabetes,
resulting in 41,463 individuals with data for the current
analyses (Fig. 1).
Data collection Information on age, sex, educational attain-
ment, marital status and zygosity was obtained from the
SALT survey [19]. All twins were categorised as monozygot-
ic, dizygotic or of undetermined zygosity. Education was
defined as the maximum years of formal schooling attained,
and dichotomised into <8 vs 8 years. Marital status was
defined as married/cohabiting vs single (including divorced
and widows/widowers).
Information on history of type 2 diabetes and heart disease
was derived from the National Patient Registry (NPR), which
covers all inpatient diagnoses in Sweden from the 1960s to the
end of 2014, and outpatient (specialist clinic) diagnoses since
2001. Each medical record in the NPR included up to eight
discharge diagnoses according to the ICD. The seventh revi-
sion (ICD-7) was used up to 1968, the eighth revision (ICD-8)
from 1969 to 1986, the ninth revision (ICD-9) from 1987 to
1996 and the tenth revision (ICD-10) since 1997.
All participants provided informed consent. The data
collection procedures were approved by the Regional Ethics
Committee at Karolinska Institutet, Stockholm, Sweden, and
by the Institutional Review Board of the University of
Southern California, USA.
Ascertainment of type 2 diabetes Type 2 diabetes was
ascertained based on self- and informant-reported history of
diabetes, glucose-lowering medication use or the NPR (ICD-7
code 260; ICD-8 and -9 code 250; and ICD-10 codes E10
E14). The age at type 2 diabetes onset was estimated accord-
ing to the earliest recorded date of type 2 diabetes in the NPR
or the date of type 2 diabetes onset available in SALT.
Assessment of heart disease Information on heart disease
diagnoses (ICD-7 codes 420, 433 and 434; ICD-8 and -9
codes 410414, 427 and 428; and ICD-10 codes I20I25
and I48I50) was obtained from the NPR. According to the
ICD codes, the major subtypes of heart disease included: (1)
coronary heart disease: angina pectoris, acute myocardial
infarction, chronic ischaemic heart disease and other coronary
heart disease (such as coronary thrombosis and Dresslers
syndrome); (2) cardiac arrhythmias: atrial fibrillation and flut-
ter, and other cardiac arrhythmias (such as ventricular fibrilla-
tion and flutter, atrial premature depolarisation and junctional
premature depolarisation); and (3) heart failure: congestive
heart failure, left ventricular failure and unspecified heart fail-
ure. The age of heart disease onset was estimated as the earli-
est date that a heart disease diagnosis was recorded in the
NPR.
Assessment of lifestyle-related factors Information on
smoking status, alcohol consumption, physical activity and
BMI was obtained from the SALT survey. Smoking status
was dichotomised as never vs ever being a smoker. Data on
alcohol consumption were collected by a question on drinking
habits, Think about your use of alcohol over your entire life.
Has there ever been a period in your life when you drank too
much?, with two response options: (1) no; and (2) yes.We
defined noas no/mild drinkingand yesas heavy drink-
ing. Data on physical activity were collected by a question on
average exercise, with seven response options: (1) almost
never;(2)much less than average;(3)less than average;
(4) average;(5)more than average;(6)much more than
average;and(7)maximum[20]. For the analyses, we
combined these categories into two groups and defined
lowas exercise almost neverto much less than average,
and regularphysical activity as less than averageto maxi-
mum. BMI was calculated as weight (kg) divided by height
squared (m
2
), and was categorised as non-overweight (BMI
<25) and overweight (BMI 25).
In the current study, we considered four healthy lifestyle-
related factors: being a non-smoker, no/mild alcohol
532 Diabetologia (2021) 64:530–539
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consumption, regular physical activity and being non-over-
weight. Participants were divided into three groups according
to the number of lifestyle-related factors: (1) unfavourable:
participants who had no or only one healthy lifestyle factor;
(2) intermediate: those who had any two or three healthy life-
style factors; and (3) favourable: those who had four healthy
lifestyle factors.
Statistical analysis The characteristics of participants in differ-
ent groups were compared using χ
2
tests, ttest and Mann
Whitney test. Generalised estimating equation (GEE) models
were used to analyse the unmatched casecontrol data while
controlling for the clustering of twins within a pair. To exam-
ine the associations between type 2 diabetes and risk of heart
disease independently, we looked at the first onset of one
specific subtype of heart disease with no others. Data for the
co-twin control study were analysed by using conditional
logistic regression, in which twin pairs were discordant for
outcome; thus, cases and control participants were comparable
with respect to early-life familial environmental factors (such
as shared childhood socioeconomic status and adolescent
environment) and genetic background (monozygotic twins
shared 100% of their genetic background and dizygotic twins
shared only 50%) [15]. In both GEE and conditional logistic
regression, the ORs and 95% CIs were estimated for the asso-
ciation between type 2 diabetes and heart disease.
Logistic regression was used to test the difference in ORs
from GEE models and conditional logistic regression by
examining the difference between the proportions of type 2
diabetes in unmatched control participants and in co-twin
control participants [2124]. Absence of a statistically
significant difference in ORs from the GEE and condition-
al logistic regression analyses suggests that genetic and
early-life familial environmental factors might not account
for the observed associations. In contrast, a statistically
significant difference in ORs from the GEE and condition-
al logistic regression analyses indicates that genetic and/or
shared environmental factors likely play a role in the
observed associations [15,2125].
The combined effect of the type 2 diabetes and lifestyle on
heart disease risk was assessed by creating dummy variables
based on the joint exposures to both factors. The presence of
an additive interaction was examined by estimating the rela-
tive excess risk due to interaction (RERI), the attributable
proportion (AP) and the synergy index (SI). Additionally,
we examined multiplicative interaction by incorporating the
two variables and their cross-product term in the same model.
Age, sex, education, BMI, smoking, alcohol consumption,
marital status and physical activity were considered as poten-
tial confounders in the type 2 diabetesheart disease associa-
tion. Missing values on education (n= 1217), smoking (n=
1167), alcohol consumption (n= 1261), BMI (n= 1918),
marital status (n= 755) and physical activity (n= 5938) were
imputed by chained equation to obtain valid statistical infer-
ences with five completed datasets generated. All statistical
analyses were performed using SAS statistical software
version 9.4 (SAS Institute, Cary, NC, USA) and IBM SPSS
Statistics 24.0 (IBM Corp, New York, NY, USA).
44,919 individual twins participated in the screening (1998–2002)
41,463 individual twins in the analysis (followed up to December 2014)
2304 (5.5%) with type 2 diabetes
9262 (22.3%) with incident heart disease
9262 heart disease cases
32,201 control participants
Unmatched case–control analyses
GEE model
Co-twin control analyses
conditional lo
g
istic re
g
ression
3184 had heart disease before screening
272 had type 1 diabetes
3808 heart disease-
discordant twin pairs
Fig. 1 Flowchart of the study
population
533Diabetologia (2021) 64:530–539
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Results
Characteristics of the study population Among all partici-
pants, 18,838 (45.4%) were men and 22,625 (54.6%) were
women (χ
2
= 30.95, p< 0.001). In total, 2304 (5.5%) had type
2 diabetes. Compared with type 2 diabetes-free participants,
those with type 2 diabetes were more likely to be older, male,
single and non-smokers; to engage in low levels of physical
activity; and to have lower educational attainment and higher
BMI (Table 1).
Association between type 2 diabetes and heart disease in
unmatched casecontrol analyses During 19982014, 9262
(22.3%) participants had incident heart disease. Compared
with type 2 diabetes-free participants, the multi-adjusted OR
for any heart disease associated with type 2 diabetes was 4.36
(95% CI 3.95, 4.81); for angina pectoris, OR 4.23 (95% CI
3.62, 4.94); for acute myocardial infarction, OR 4.93 (95% CI
4.25, 5.72); for chronic ischaemic heart disease, OR 5.14
(95% CI 3.82, 6.91); for atrial fibrillation and flutter, OR
3.14 (95% CI 2.71, 3.64); for congestive heart failure, OR
5.76 (95% CI 3.96, 8.38); and for left ventricular failure, OR
4.45 (95% CI 2.65, 7.49) (Table 2).
Association between type 2 diabetes and heart disease in co-
twin control analyses Compared with the OR in GEE
models, the association between type 2 diabetes and
heart disease became stronger (OR 4.89; 95% CI 3.88,
6.16) in the co-twin control analyses (including all twin
pairs). The difference in ORs from the GEE models
based on unmatched casecontrol analyses vs co-twin
control analyses in all twin pairs was statistically signif-
icant (OR 1.57; 95% CI 1.42, 1.73; p< 0.001). In addi-
tion, the multi-adjusted OR (95% CI) of heart disease
associated with type 2 diabetes was 4.07 (3.15, 5.27) in
dizygotic twins and 10.83 (4.67, 25.10) in monozygotic
twins. These results suggest that type 2 diabetes is still
associated with heart disease, even after fully control-
ling for genetic and early-life familial environmental
factors (Table 3).
Association between lifestyle-related factors and heart
disease In multi-adjusted GEE models, being a non-smoker,
regular physical activity, no/mild drinking and being non-
overweight were associated with a decreased risk of heart
disease. In further analysis, an intermediate lifestyle and a
favourable lifestyle were significantly associated with a lower
risk of heart disease (Table 4).
In stratified analyses by type 2 diabetes, compared with an
unfavourable lifestyle, an intermediate lifestyle or a
favourable lifestyle was associated with a significant 32%
(OR 0.68; 95% CI 0.49, 0.93) or 56% (OR 0.44; 95% CI
0.30, 0.63) decrease in heart disease risk among patients with
type 2 diabetes, respectively (Fig. 2and electronic supplemen-
tary material [ESM] Table 1).
Joint effect of type 2 diabetes and lifestyle-related factors on
heart disease risk In joint effect analyses, there was a significant
additive interaction between type 2 diabetes and lifestyle on heart
disease risk (RERI 3.507; 95% CI 0.929, 6.084; AP 0.414; 95%
CI 0.231, 0.597; SI 1.885; 95% CI 1.318, 2.696) (ESM Table 2).
The multi-adjusted OR for type 2 diabetes multiplied by
unfavourable lifestyle was 1.30 (95% CI 1.07, 1.57; p= 0.008)
for heart disease.
Supplementary analysis Considering possible sex differ-
ences in heart disease development, we performed strat-
ified analysis, and the associations between type 2
diabetes and heart disease risk did not vary by sex
(ESM Table 3). The results were not much altered
compared with those from initial analyses when we
repeated analyses: (1) with additional adjustment for
survival status (ESM Table 4); and (2) excluding miss-
ing values for covariates (ESM Table 5).
Table 1 Baseline characteristics of the study participants by type 2
diabetes status (N= 41,463)
Characteristic T2D-free
n= 39,159
T2D
n=2304
pvalue
Age (years), mean ± SD 58.1 ± 10.6 64.7 ± 10.5 <0.001
Male sex, n(%) 17,662 (45.1) 1176 (51.0) <0.001
Education, n(%) <0.001
<8 years 12,510 (32.0) 1091 (47.4)
8 years 26,649 (68.0) 1213 (52.6)
Marital status, n(%) <0.001
Married/cohabiting 28,626 (73.1) 1487 (64.5)
Single 10,533 (26.9) 817 (35.5)
Zygosity, n(%) 0.879
Monozygotic 7759 (19.8) 458 (19.9)
Dizygotic 26,233 (67.0) 1534 (66.6)
Undetermined 5167 (13.2) 312 (13.5)
BMI, mean ± SD 24.8 ± 3.4 26.9 ± 4.1 <0.001
<25 (Non-overweight) 21,880 (55.9) 768 (33.3) <0.001
25 (Overweight) 17,279 (44.1) 1536 (66.7)
Smoking status, n(%) 0.024
Never 19,058 (48.7) 1177 (51.1)
Ever a smoker 20,101 (51.3) 1127 (48.9)
Alcohol consumption, n(%) 0.247
No/mild drinking 36,204 (92.5) 2115 (91.8)
Heavy drinking 2955 (7.5) 189 (8.2)
Physical activity, n(%) 0.007
Low 3905 (10.0) 270 (11.7)
Regular 35,254 (90.0) 2034 (88.3)
Data are presented as mean ± SD or number (proportion, %)
T2D, type 2 diabetes
534 Diabetologia (2021) 64:530–539
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Discussion
In this large-scale, nationwide, genetically informative sample
of Swedish twins, we found that type 2 diabetes was indepen-
dently associated with increased risk of heart disease and its
major types, specifically angina pectoris, acute myocardial
infarction, chronic ischaemic heart disease, atrial fibrillation
and flutter, and heart failure. The association remained signif-
icant, even after controlling for genetic and early-life familial
environmental factors. However, a healthy lifestyle might
significantly mitigate the risk of heart disease related to type
2 diabetes compared with an unfavourable lifestyle.
In recent decades, many epidemiologic studies have shown
that type 2 diabetes is associated with a two- to sixfold
increased risk of total CVD and coronary heart disease
[2,46]. However, the association between type 2 diabetes
and atrial fibrillation has been addressed in a number of epide-
miologic studies with inconclusive results. Some studies
showed an increased risk of atrial fibrillation among people
with type 2 diabetes [8,9,12], but others indicated no clear
association [10,11]. In a recent meta-analysis of 32 cohort
studies, type 2 diabetes was associated with a modest 30%
increased atrial fibrillation risk [26]. In the present study, we
found that type 2 diabetes conferred a more than fourfold
greater risk of coronary heart disease and a doubled atrial
fibrillation risk. Several studies have shown that type 2 diabe-
tes is positively associated with heart failure, but in most of
these the influences of other subtypes of heart disease were not
Table 2 ORs and 95% CIs of
different forms of heart disease
related to type 2 diabetes from
GEE models (type 2 diabetes-free
as the reference)
Heart disease No. of cases OR (95% CI)
a
OR (95% CI)
b
All types 9262 4.71 (4.27, 5.19) 4.36 (3.95, 4.81)
Coronary heart disease 4403 5.14 (4.58, 5.78) 4.83 (4.30, 5.43)
Angina pectoris 1936 4.53 (3.88, 5.29) 4.23 (3.62, 4.94)
Acute myocardial infarction 2089 5.20 (4.49, 6.03) 4.93 (4.25, 5.72)
Chronic ischaemic heart disease 362 5.49 (4.09, 7.37) 5.14 (3.82, 6.91)
Other coronary heart disease 16 15.08 (4.85, 46.86) 15.39 (4.69, 50.49)
Cardiac arrhythmias 3471 3.35 (2.92, 3.84) 3.14 (2.74, 3.60)
Atrial fibrillation and flutter 2835 3.40 (2.94, 3.94) 3.14 (2.71, 3.64)
Other cardiac arrhythmias 636 3.03 (2.28, 4.03) 3.04 (2.28, 4.04)
Heart failure 1388 5.31 (4.45, 6.34) 4.89 (4.09, 5.84)
Congestive heart failure 181 6.29 (4.30, 9.21) 5.76 (3.96, 8.38)
Left ventricular failure 110 4.92 (2.91, 8.29) 4.45 (2.65, 7.49)
Unspecified heart failure 1097 4.86 (4.01, 5.90) 4.52 (3.72, 5.49)
a
Adjusted for age, sex and education
b
Additionally adjusted for marital status, BMI, smoking, alcohol consumption and physical activity
Table 3 ORs and 95% CIs for the
association between type 2
diabetes and heart disease in co-
twin control analyses using
conditional logistic regression
Co-twin without heart disease Co-twin with heart disease
All types
a
Dizygotic only Monozygotic only
T2D-free T2D T2D-free T2D T2D-free T2D
T2D-free 3193 464 2278 337 588 65
T2D 90 6176 366 17
Basic-adjusted OR (95% CI)
b
5.07 (4.04, 6.38) 4.32 (3.35, 5.56) 10.88 (4.71, 25.11)
Multi-adjusted OR (95% CI)
c
4.89 (3.88, 6.16) 4.07 (3.15, 5.27) 10.83 (4.67, 25.10)
a
Including dizygotic twins, monozygotic twins and twins of undetermined zygosity. The 3808 heart disease-
discordant pairs were divided into four groups with respect to exposure (T2D) status. In 3193 twin pairs, both
were T2D-free. In 61 twin pairs, both had T2D. In 464 twin pairs, the healthy (heart disease-free) co-twin was
T2D-free and the diseased twin had T2D.In 90 twin pairs, the diseased co-twin was T2D-free and the healthy twin
had T2D
b
Adjusted for sex and education
c
Adjusted for sex, education, marital status, BMI, smoking, alcohol consumption and physical activity
T2D, type 2 diabetes
535Diabetologia (2021) 64:530–539
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taken into account [2,27,28]. As the onset and progression of
angina pectoris, acute myocardial infarction and atrial fibrilla-
tion may also contribute to heart failure, we looked at the first
onset of heart failure with no previous coronary heart disease
and cardiac arrhythmias and found that the higher risk of heart
failure with type 2 diabetes was independent of other specific
subtypes of heart disease.
Accumulating evidence has shown that molecular defects,
intrauterine environment and socioeconomic factors are asso-
ciated with the development of type 2 diabetes, and also
contribute to an increased risk of heart disease [13,29].
Twins are generally raised together and share the same genetic
background as well as intrauterine, childhood and adolescent
environments. Twin studies provide us with an opportunity to
investigate whether the association between type 2 diabetes
and heart disease is potentially confounded by genetic and/or
early-life familial environmental backgrounds. In the present
study, results of co-twin control analyses implicate that type 2
diabetes is still associated with an increased risk of heart
disease, even after fully controlling for genetic and early-life
familial environmental backgrounds.
Thus far, previous studies have mainly focused on the
combined effect of an overall healthy lifestyle and type 2
diabetes on mortality or total CVD (including coronary heart
disease, stroke and peripheral vascular disease) risk, but data
specific for only heart disease risk are limited. One
population-based prospective cohortstudy of Chinese patients
with type 2 diabetes showed that active smoking, physical
inactivity, alcohol drinking and high carbohydrate intake
increased the risk of all-cause mortality and CVD mortality
after a mean follow-up of 4.02 years of follow-up [17].
Another prospective study including 11,527 participants with
type 2 diabetes suggested that an overall healthy lifestyle (diet,
smoking status, alcohol consumption and physical activity)
was associated with substantially lower risks of CVD inci-
dence (including stroke and coronary heart disease) and
CVD mortality during a mean follow-up of 13.3 years of
follow-up [18]. In contrast, at a median follow-up of almost
10 years, a multicentre randomised clinical trial found that an
intensive lifestyle intervention (diet modification and
increased physical activity) could produce improvements in
CVD risk factors (such as blood pressure and high-density
lipoprotein cholesterol levels) in individuals with type 2
diabetes, but not reduce CVD events (including stroke and
coronary heart disease) [30]. The discrepancy in findings
Table 4 ORs and 95% CIs of
heart disease in relation to BMI,
smoking status, alcohol
consumption and physical activi-
ty from GEE models
Lifestyle factor No. of cases Heart disease OR (95% CI)
a
Heart disease OR (95% CI)
b
BMI
25 (overweight) 4955 Reference Reference
<25 (non-overweight) 4307 0.71 (0.68, 0.75) 0.77 (0.74, 0.81)
Smoking
Yes 4697 Reference Reference
No 4565 0.86 (0.81, 0.90) 0.86 (0.82, 0.91)
Alcohol consumption
Heavy drinking 710 Reference Reference
No/mild drinking 8552 0.83 (0.76, 0.91) 0.89 (0.81, 0.98)
Physical activity
Low 1032 Reference Reference
Regular 8230 0.78 (0.72, 0.84) 0.82 (0.76, 0.89)
Lifestyle
Unfavourable 693 Reference Reference
Intermediate 6638 0.70 (0.64, 0.77) 0.73 (0.66, 0.81)
Favourable 1931 0.49 (0.44, 0.55) 0.54 (0.48, 0.60)
a
Adjusted for age, sex and education
b
Adjusted for age, sex, education, marital status and type 2 diabetes, as well as BMI, smoking, alcohol consump-
tion and physical activity, if applicable
1.00
0.68
0.44
Unfavourable Intermediate Favourable
0
0.2
0.4
0.6
0.8
1.0
1.2
ORs of heart disease
lifestyle
Fig. 2 Multi-adjusted ORs (95% CIs) of heart disease in relation to life-
style among patients with type 2 diabetes from GEE models (adjusted for
age, sex, education and marital status)
536 Diabetologia (2021) 64:530–539
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might reflect differences in follow-up times, lifestyle factors
and definitions of outcome. To the best of our knowledge, the
current study is the first to provide evidence that a healthy
lifestyle consisting of being a non-smoker, no/mild alcohol
consumption, regular physical activity and being non-
overweight may greatly attenuate the risk of heart disease in
type 2 diabetes. In the current study, patients with type 2
diabetes who reported maintaining not only a favourable (four
healthy lifestyle factors) but also an intermediate lifestyle (any
two or three healthy lifestyle factors) had a significantly lower
heart disease risk than those with an unfavourable lifestyle (no
or only one healthy lifestyle factor).
The mechanisms responsible for the increased heart disease
morbidity attributable to type 2 diabetes are multifactorial and
incompletely understood. An important role of metabolic
disturbances, such as long-term hyperglycaemia, insulin resis-
tance and dyslipidaemia, has been hypothesised [31,32].
Accelerated atherosclerosis and thrombosis in patients with
type 2 diabetes principally result from inflammation, reactive
oxygen species and endothelial dysfunction combined with
coagulation, platelet abnormalities and impaired fibrinolysis
[33]. Type 2 diabetes leads to autonomic dysfunction and
structural remodelling of the left atrium in the form of atrial
dilatation and interstitial fibrosis, which might contribute to
life-threatening arrhythmias [26]. In addition, how a
favourable lifestyle mitigates the risk of heart disease among
participants with or without type 2 diabetes may be explained
by multiple possible mechanismsan overall healthy lifestyle
can improve glycaemic control, insulin sensitivity, blood pres-
sure, platelet function, lipid profile and body composition
[16,17,34].
There are several strengths and limitations in the current
study. First, the large, nationwide, population-based twin
cohort provided us with a unique opportunity to further exam-
ine the effect of type 2 diabetes on heart disease risk while
controlling for some unmeasured confounders such as genetic
and early-life familial environmental factors. Second, we used
GEE modelling, which is more appropriate than logistic
regression models in casecontrol design, since it accounts
for the clustering of twins within a pair. Nonetheless, the limi-
tations in our study need to be pointed out. First, blood glucose
level was not available in the STR or SALT. Consequently,
given the higher prevalence of undiagnosed type 2 diabetes in
elderly people [35], subjects with undiagnosed type 2 diabetes
might have been misclassified as type 2 diabetes-free,
which might have led to an underestimation of the
observed associations. Second, type 2 diabetes and heart
disease were associated with mortality risk, which may
contribute to under- or over-estimation of the observed
associations. In the current study, we repeated the analyses
with an additional adjustment for survival status, and the
results were not substantially altered. Third, because infor-
mation on lifestyle factors was obtained at baseline, it is
difficult to capture potential variations in lifestyle factors
during follow-up, which would result in underestimation
for the effect. Fourth, although some lifestyle-related factors
such as smoking, alcohol consumption and physical activity
were taken into account, information on diet, sleep duration
and other lifestyle-related factors was not available. Finally,
information bias might have occurred due to self-reported
information on lifestyle-related factors. This might have
caused non-differential misclassification leading to underes-
timation for the observed association.
Conclusions In conclusion, our study provides further
evidence that type 2 diabetes is associated with about fourfold
greater risk of heart disease, including coronary heart disease,
cardiac arrhythmias and heart failure. Moreover, the associa-
tion between type 2 diabetes and heart disease remains statis-
tically significant, even after fully controlling for genetic and
early-life familial environmental background. Patients with
type 2 diabetes who reported maintaining a healthy lifestyle
consisting of being a non-smoker, no/mild alcohol consump-
tion, regular physical activity and being non-overweight had a
significantly lower heart disease risk than those with an
unfavourable lifestyle. Our findings highlight the importance
of a healthy lifestyle in prevention of heart disease among
patients with type 2 diabetes.
Acknowledgements We are grateful to all the twins who took part in the
study and to the members of the survey teams. The Swedish Twin
Registry is managed by Karolinska Institutet and receives funding
through the Swedish Research Council under grant no. 2017-00641.
Data availability Raw data are available by request from qualified inves-
tigators applying to the Swedish Twin Registry.
Funding Open access funding provided by Karolinska Institute. This
work was supported by the Swedish Research Council (no. 2017-
00981), the National Natural Science Foundation of China (no.
81771519), the Konung Gustaf V:s och Drottning Victorias Frimurare
Foundation (no. 2016-2017), Demensfonden, Strokefonden, Cornells
Stiftelse and Alzheimerfonden (2017-2018). This project is part of
CoSTREAM (www.costream.eu) and received funding from the
European Unions Horizon 2020 research and innovation programme
under grant agreement no. 667375.
Authorsrelationships and activities The authors declare that there are
no relationships or activities that might bias, or be perceived to bias, their
work.
Contribution statement RY and WX had full access to all the data in the
study and take responsibility for the integrity of the data and the accuracy
of the data analysis. WX and XQ were involved in study concept and
design. RY and HX did the statistical analysis and drafted the manuscript.
NLP was involved in acquisition of data and had full access to all the data
in the study. XL, JY and CB contributed to analysis and interpretation of
data. All authors contributed to critical revision of the manuscript for
important intellectual content. WX obtained funding for the study. WX
and XQ were involved in study supervision. All authors gave their final
approval of the version to be published.
537Diabetologia (2021) 64:530–539
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... Alcohol consumption was categorized as no/mild drinking or heavy drinking. Physical activity was defined based on a question about annual exercise patterns and grouped as active (including the responses 'more than average', 'much more than average' and 'maximum') and inactive (including the responses 'almost never', 'much less than average', 'less than average' and 'average') [23]. Body mass index (BMI) was calculated as weight in kilograms divided by the square of height in meters (kg/m 2 ) and classified as underweight (<20.0), ...
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Background and aims Public health and clinic-based educational strategies are desperately needed to stem the tide of death from heart disease among people with diabetes in low and middle-income countries. This study translated the Heart Disease Fact Questionnaire into Persian and evaluated its reliability and validity for use in Iran. Methods Using rigorous translation methods, the 25-item scale was administered to Persian speakers with diabetes. The scale was evaluated for content validity, construct validity and reliability. Results Participants were 268 patients with diabetes with mean age of 63.19 ± 16.61 years. The mean HDFQ score was 17.31 ± 5.11 (in the low range). Higher scores were associated with younger age, younger age of diabetes onset, higher education, higher employment position, family history of diabetes and hypertension, shorter diabetes duration, and adherence to home exercise regimens. Kuder–Richardson's reliability coefficient was good, i.e., 0.82. Confirmatory factor analysis showed that the factor loadings of all questions, except question number 25, were favorable, i.e., >0.3. Model fit indices were favorable: Chi-square statistic to degree of freedom ratio (χ²⁄df) = 1.82, Comparative fit index = 0.96, Tucker-Lewis Index = 0.96 and root mean square error = 0.06. Conclusion After removing item #25, the Persian heart disease fact questionnaire has good validity and reliability and can be used to inform and evaluate clinical and public health educational programs aimed at decreasing risk for heart disease among Persian speakers with diabetes.
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Background: Whether lifestyle factors are similarly associated with risk of heart failure (HF) for individuals with different metabolic or genetic risk status remains unclear. Methods: We included 464 483 participants from UK Biobank who were free of major cardiovascular disease or HF during baseline recruitment. Healthy lifestyle factors included avoidance of smoking, no obesity, regular physical activity, and healthy diet. Lifestyle was categorized as favorable (3 or 4 healthy lifestyle factors), intermediate (2 healthy lifestyle factors), and unfavorable (0 or 1 healthy lifestyle factor) lifestyles. Metabolic status was defined by the presence of hypertension, high total cholesterol, or diabetes at baseline. A weighted genetic risk score was created based on 12 single-nucleotide polymorphisms associated with HF. Results: Compared with favorable lifestyle, the multivariable-adjusted hazard ratios of HF were 1.79 (95% CI, 1.68-1.90) and 2.90 (95% CI, 2.70-3.11) for intermediate lifestyle and unfavorable lifestyle, respectively (Ptrend <0.0001). This association was largely consistent regardless of the presence of any single metabolic risk factor or the number of metabolic risk factors (Pinteraction ≥0.21). The association was also similar across different genetic risk categories (Pinteraction=0.92). In a joint analysis, the hazard ratio of HF was 4.05 (95% CI, 3.43-4.77) comparing participants who had both higher genetic risk and an unfavorable lifestyle with those having lower genetic risk and a favorable lifestyle. Conclusions: Combined lifestyle was associated with incident HF regardless of metabolic or genetic risk status, supporting the recommendation of healthy lifestyles for HF prevention across the entire population.
Article
Background: Although age at menopause has been linked to mortality, the association between the entire reproductive lifespan and mortality remains unclear. Objectives: To examine to what extent life-course reproductive duration is associated with all-cause mortality and explore the role of a healthy lifestyle and familial background in such association. Study design: From the Swedish Twin Registry, 11,669 female individuals (mean age: 63.54 years) were followed for up to 19 years. Information on reproductive duration (the interval between ages at menarche and menopause) and lifestyle factors (including smoking, alcohol consumption, and physical activity; divided into unfavorable/intermediate/favorable) was collected based on a structured questionnaire. Survival status was obtained from the Sweden Cause of Death Register. Data were analyzed using generalized estimating equation models, Laplace regression, and conditional logistic regression. Results: In the generalized estimating equation model, compared to those with ≤34 reproductive years, the odds ratio (95% confidence interval) of all-cause mortality was 0.79 (0.68-0.90) for those with ≥40 reproductive years, which prolonged survival time by 0.84 (0.24-1.43) years. Women with ≥40 reproductive years plus a favorable lifestyle (odds ratio=0.28, 95% confidence interval:0.23-0.35) were at a lower risk of all-cause mortality compared to those with <40 reproductive years plus an unfavorable lifestyle. An additive interaction between ≥40 reproductive years and a favorable lifestyle on all-cause mortality was observed (attributable proportion=0.584, 95% confidence interval:0.016-1.151). The odds ratios in conditional logistic regression and generalized estimating equation models did not differ significantly (P=0.67). Conclusions: Longer reproductive lifespan is associated with reduced all-cause mortality and prolongs survival by 0.84 years. A favorable lifestyle may amplify the beneficial effect of longer reproductive lifespan on mortality. Familial background does not account for the observed association.
Article
Aim/introduction: We investigated the associations between a combination of lifestyle factors and changes to these factors and the subsequent risk of severe hypoglycemia (SH) in type 2 diabetes (T2D). Materials and methods: Subjects with adult T2D who underwent consecutive two-year interval health screening programs from 2009 to 2012 from the Korean National Health Insurance Service database were included and followed up until 2018. Information on history of smoking status, alcohol consumption, and physical activity as well as changes to these factors was obtained. The primary outcome was incident SH. Results: Of the 1,490,233 T2D subjects, 30,539 (2.1%) subjects developed SH. Current smokers and heavy drinkers had increased risk of SH, compared to nonsmokers and nondrinkers, respectively (hazard ratio (HR) 1.28 [1.23-1.34]; HR 1.22 [1.15-1.30]). However, regular physical activity was associated with reduced SH risk (HR 0.79 [0.77-0.82]). A combination of unhealthy lifestyle habits was associated with increased SH risk in a dose-dependent fashion (P for trend <0.001). Compared with subjects without changes in their unhealthy lifestyles, subjects who improved lifestyles had decreased risk of SH. Conclusions: Greater adherence to healthy lifestyle factors and any improvement in unhealthy lifestyle habits were associated with a substantially lower risk of SH in individuals with T2D.
Chapter
Diabetes is het Latijnse woord voor een hoge urineproductie, mellitus betekent zoet. De onderverdeling in type 1 en 2 stamt uit de jaren dertig van de vorige eeuw. Diabetes mellitus type 2 (DM2) werd eerder ook ouderdoms- of niet-insulineafhankelijke diabetes genoemd. Diabetes is gedefinieerd als een herhaalde nuchtere plasmaglucosewaarde boven de 7,0 mmol/l of een willekeurige waarde boven de 11,1 mmol/l, in combinatie met klachten die passen bij hyperglykemie, zoals extreme dorst en overmatig moeten plassen (polydipsie en polyurie). DM2 kenmerkt zich bij veel mensen door insulineresistentie (IR), mede als gevolg van een overmaat aan energie in visceraal vet, lever en spierweefsel, waarbij de pancreas niet meer in staat is voldoende insuline te maken om de bloedglucosespiegel normaal te houden. Pas als laat fenomeen stellen we via hyperglykemie de diagnose DM2 in de praktijk.
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Aims/hypothesis: We aimed to examine the association between midlife type 2 diabetes mellitus and cerebrovascular disease (CBD) in late life, and further to explore whether genetic and early-life familial environmental factors (such as shared childhood socioeconomic status and adolescent environment) play a role in this association. Methods: In this prospective nested case-control study based on the Swedish Twin Registry, 33,086 twin individuals who were born in 1958 or earlier and were CBD-free before the age of 60 were included. Midlife (40-59 years) type 2 diabetes was ascertained from self-report, the National Patient Registry (NPR) and glucose-lowering medication use. CBD diagnosis (cerebral infarction, occlusion of cerebral arteries, subarachnoid haemorrhage, intracerebral haemorrhage and unspecified CBD) and onset age were identified from the NPR. Late-life CBD was defined as CBD onset age ≥60 years. Generalised estimating equation (GEE) models were used to analyse unmatched case-control data (adjusted for the clustering of twins within a pair). Conditional logistic regression was used in co-twin matched case-control analyses in CBD-discordant twin pairs. Results: Of all the participants, 1248 (3.8%) had midlife type 2 diabetes and 3121 (9.4%) had CBD in late life. In GEE models adjusted for age, sex, education, BMI, smoking, alcohol consumption, marital status, hypertension and heart disease, the ORs (95% CIs) of type 2 diabetes were 1.29 (1.03, 1.61) for cerebral infarction, 2.03 (1.20, 3.44) for occlusion of cerebral arteries, 0.52 (0.12, 2.21) for subarachnoid haemorrhage and 0.78 (0.45, 1.36) for intracerebral haemorrhage. In multi-adjusted conditional logistic regression, the OR of the type 2 diabetes-cerebral infarction association was 0.96 (0.51, 1.80). The differences in ORs from the GEE and co-twin control analyses were not statistically significant (p = 0.780). Conclusions/interpretation: Midlife type 2 diabetes is significantly associated with increased risk of cerebral infarction and occlusion of cerebral arteries, but not intracerebral haemorrhage or subarachnoid haemorrhage in late life. Genetic and early-life familial environmental factors do not appear to account for the type 2 diabetes-cerebral infarction association, but further clarification is needed.
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Background Evidence is limited regarding the impact of healthy lifestyle practices on the risk of subsequent cardiovascular events among patients with diabetes. Objectives The purpose of this study was to examine the associations of an overall healthy lifestyle, defined by eating a high-quality diet (top two-fifths of Alternative Healthy Eating Index), nonsmoking, engaging in moderate- to vigorous-intensity physical activity (≥150 min/week), and drinking alcohol in moderation (5 to 15 g/day for women and 5 to 30 g/day for men), with the risk of developing cardiovascular disease (CVD) and CVD mortality among adults with type 2 diabetes (T2D). Methods This prospective analysis included 11,527 participants with T2D diagnosed during follow-up (8,970 women from the Nurses’ Health Study and 2,557 men from the Health Professionals Follow-Up Study), who were free of CVD and cancer at the time of diabetes diagnosis. Diet and lifestyle factors before and after T2D diagnosis were repeatedly assessed every 2 to 4 years. Results There were 2,311 incident CVD cases and 858 CVD deaths during an average of 13.3 years of follow-up. After multivariate adjustment of covariates, the low-risk lifestyle factors after diabetes diagnosis were each associated with a lower risk of CVD incidence and CVD mortality. The multivariate-adjusted hazard ratios for participants with 3 or more low-risk lifestyle factors compared with 0 were 0.48 (95% confidence interval [CI]: 0.40 to 0.59) for total CVD incidence, 0.53 (95% CI: 0.42 to 0.66) for incidence of coronary heart disease, 0.33 (95% CI: 0.21 to 0.51) for stroke incidence, and 0.32 (95% CI: 0.22 to 0.47) for CVD mortality (all p trend <0.001). The population-attributable risk for poor adherence to the overall healthy lifestyle (<3 low-risk factors) was 40.9% (95% CI: 28.5% to 52.0%) for CVD mortality. In addition, greater improvements in healthy lifestyle factors from pre-diabetes to post-diabetes diagnosis were also significantly associated with a lower risk of CVD incidence and CVD mortality. For each number increment in low-risk lifestyle factors there was a 14% lower risk of incident total CVD, a 12% lower risk of coronary heart disease, a 21% lower risk of stroke, and a 27% lower risk of CVD mortality (all p < 0.001). Similar results were observed when analyses were stratified by diabetes duration, sex/cohort, body mass index at diabetes diagnosis, smoking status, and lifestyle factors before diabetes diagnosis. Conclusions Greater adherence to an overall healthy lifestyle is associated with a substantially lower risk of CVD incidence and CVD mortality among adults with T2D. These findings further support the tremendous benefits of adopting a healthy lifestyle in reducing the subsequent burden of cardiovascular complications in patients with T2D.
Article
This study examined whether midlife overweight (body mass index [BMI] ≥25) is associated with late‐life cancer risk and explored the role of genetic and early‐life environmental factors in this association. The study included 14,766 individuals from the Swedish Twin Registry, whose midlife (30–50 years) height and weight were recorded. Information on cancer diagnoses in late life (>65 years) was derived from the National Patient Registry and Cancer Registry. Generalized estimating equation (GEE) models were used to analyze unmatched case‐control data (controlled for the clustering of twins within a pair). A co‐twin matched case‐control analysis used conditional logistic regression to compare cancer‐discordant twins. Of all participants, 3,968 (26.9%) were overweight and 4,253 (28.8%) had cancer. In multi‐adjusted GEE models using normal‐weight (BMI 18.5–24.9) participants as the reference group, overweight was related to higher risk of colon cancer (OR 1.36, 95% CI: 1.00‐1.84, P=0.049), liver cancer (OR 2.00, 95% CI: 1.11‐3.62), cervix uteri cancer (OR 2.86, 95% CI: 1.19‐6.91), and corpus uteri cancer (OR 1.78, 95% CI: 1.14‐2.78) but lower risk of non‐melanoma skin cancer (OR 0.77, 95% CI: 0.66‐0.90). In conditional logistic regression analysis, these associations were attenuated becoming non‐significance. The difference in ORs from the unmatched and matched analyses was not significant. In conclusion, midlife overweight is associated with increased risk of late‐life colon, liver, and uterine cancer but reduced risk of late‐life non‐melanoma skin cancer. Further investigations are warranted to explore the role of genetic and early‐life environmental factors in these associations. This article is protected by copyright. All rights reserved.
Article
The association between diabetes and cancer risk remains controversial. Hence, we examined whether midlife diabetes is related to the risk of cancer in late-life, and whether genetic and early-life environmental factors play a role in this association. This study included 25,154 twin individuals born in 1958 or earlier from the Swedish Twin Registry. Information on cancer diagnosis in late life (aged ≥ 65) during 1998-2014, was derived from the National Patient and Cancer Registries. Diabetes was ascertained based on self- or informant-reported history, patient registry, and antidiabetic medication use. Midlife diabetes was defined when diabetes was diagnosed before 65 years. Data were analyzed following two strategies: 1) unmatched case-control analysis for all participants using generalized estimating equation (GEE) models, and 2) co-twin control analysis for cancer-discordant twin pairs using conditional logistic regression. Overall, 1,766 (7.0%) had midlife diabetes and 5293 (21.0%) had cancer in late-life. In multi-adjusted GEE models, the odds ratios (95% CIs) of diabetes were 10.55 (2.95-37.67) for pharynx cancer, 5.78 (1.72-19.40) for small intestine cancer, 2.37 (1.14-4.91) for liver cancer, and 0.48 (0.35-0.67) for prostate cancer. In people with diabetes, diabetes duration was dose-dependently associated with cancer risk. In conditional logistic regression analysis of 176 prostate cancer-discordant twin pairs, the association between midlife diabetes and prostate cancer in later life became stronger. Midlife diabetes increases the risk of pharynx, small intestine and liver cancers, but reduces prostate cancer risk in late life. Genetic and early-life environmental factors may partially contribute to the diabetes-prostate cancer association. This article is protected by copyright. All rights reserved.
Article
Background Diabetes and elevated blood glucose have been associated with increased risk of atrial fibrillation in a number of epidemiological studies, however, the findings have not been entirely consistent. We conducted a systematic review and meta-analysis to clarify the association. Material and methods We searched the PubMed and Embase databases for studies of diabetes and blood glucose and atrial fibrillation up to July 18th 2017. Cohort studies were included if they reported relative risk (RR) estimates and 95% confidence intervals (CIs) of atrial fibrillation associated with a diabetes diagnosis, prediabetes or blood glucose. Summary RRs were estimated using a random effects model. Results Thirty four studies were included in the meta-analysis of diabetes, pre-diabetes or blood glucose and atrial fibrillation. Thirty two cohort studies (464,229 cases, >10,244,043 participants) were included in the analysis of diabetes mellitus and atrial fibrillation. The summary RR for patients with diabetes mellitus versus patients without diabetes was 1.30 (95% CIs: 1.03–1.66), however, there was extreme heterogeneity, I² = 99.9%) and evidence of publication bias with Begg's test, p < 0.0001. After excluding a very large and outlying study the summary RR was 1.28 (95% CI: 1.22–1.35, I² = 90%, n = 31, 249,772 cases, 10,244,043 participants). The heterogeneity was mainly due to differences in the size of the association between studies and the results persisted in a number of subgroup and sensitivity analyses. The summary RR was 1.20 (95% CI: 1.03–1.39, I² = 30%, n = 4, 2392 cases, 58,547 participants) for the association between prediabetes and atrial fibrillation. The summary RR was 1.11 (95% CI: 1.04–1.18, I² = 61%, n = 4) per 20 mg/dl increase of blood glucose in relation to atrial fibrillation (3385 cases, 247,447 participants) and there was no evidence of nonlinearity, pnonlinearity = 0.34. Conclusions This meta-analysis suggest that prediabetes and diabetes increase the risk of atrial fibrillation by 20% and 28%, respectively, and there is a dose-response relationship between increasing blood glucose and atrial fibrillation. Any further studies should clarify whether the association between diabetes and blood glucose and atrial fibrillation is independent of adiposity.
Article
Each year, the American Heart Association (AHA), in conjunction with the Centers for Disease Control and Prevention, the National Institutes of Health, and other government agencies, brings together in a single document the most up-to-date statistics related to heart disease, stroke, and the cardiovascular risk factors listed in the AHA's My Life Check - Life's Simple 7 (Figure¹), which include core health behaviors (smoking, physical activity, diet, and weight) and health factors (cholesterol, blood pressure [BP], and glucose control) that contribute to cardiovascular health. The Statistical Update represents a critical resource for the lay public, policy makers, media professionals, clinicians, healthcare administrators, researchers, health advocates, and others seeking the best available data on these factors and conditions. Cardiovascular disease (CVD) and stroke produce immense health and economic burdens in the United States and globally. The Update also presents the latest data on a range of major clinical heart and circulatory disease conditions (including stroke, congenital heart disease, rhythm disorders, subclinical atherosclerosis, coronary heart disease [CHD], heart failure [HF], valvular disease, venous disease, and peripheral artery disease) and the associated outcomes (including quality of care, procedures, and economic costs). Since 2007, the annual versions of the Statistical Update have been cited >20 000 times in the literature. From January to July 2017 alone, the 2017 Statistical Update was accessed >106 500 times. Each annual version of the Statistical Update undergoes revisions to include the newest nationally representative data, add additional relevant published scientific findings, remove older information, add new sections or chapters, and increase the number of ways to access and use the assembled information. This year-long process, which begins as soon as the previous Statistical Update is published, is performed by the AHA Statistics Committee faculty volunteers and staff and government agency partners. This year's edition includes new data on the monitoring and benefits of cardiovascular health in the population, new metrics to assess and monitor healthy diets, new information on stroke in young adults, an enhanced focus on underserved and minority populations, a substantively expanded focus on the global burden of CVD, and further evidence-based approaches to changing behaviors, implementation strategies, and implications of the AHA's 2020 Impact Goals. Below are a few highlights from this year's Update.
Article
Cardiovascular disease remains the principal cause of death and disability among patients with diabetes mellitus. Diabetes mellitus exacerbates mechanisms underlying atherosclerosis and heart failure. Unfortunately, these mechanisms are not adequately modulated by therapeutic strategies focusing solely on optimal glycemic control with currently available drugs or approaches. In the setting of multifactorial risk reduction with statins and other lipid-lowering agents, antihypertensive therapies, and antihyperglycemic treatment strategies, cardiovascular complication rates are falling, yet remain higher for patients with diabetes mellitus than for those without. This review considers the mechanisms, history, controversies, new pharmacological agents, and recent evidence for current guidelines for cardiovascular management in the patient with diabetes mellitus to support evidence-based care in the patient with diabetes mellitus and heart disease outside of the acute care setting.
Article
Background: Lifestyle interventions produce short-term improvements in glycemia and cardiovascular disease (CVD) risk factors in individuals with type 2 diabetes mellitus, but no long-term data are available. We examined the effects of lifestyle intervention on changes in weight, fitness, and CVD risk factors during a 4-year study. Methods: The Look AHEAD (Action for Health in Diabetes) trial is a multicenter randomized clinical trial comparing the effects of an intensive lifestyle intervention (ILI) and diabetes support and education (DSE; the control group) on the incidence of major CVD events in 5145 overweight or obese individuals (59.5% female; mean age, 58.7 years) with type 2 diabetes mellitus. More than 93% of participants provided outcomes data at each annual assessment. Results: Averaged across 4 years, ILI participants had a greater percentage of weight loss than DSE participants (-6.15% vs -0.88%; P < .001) and greater improvements in treadmill fitness (12.74% vs 1.96%; P < .001), hemoglobin A(1c) level (-0.36% vs -0.09%; P < .001), systolic (-5.33 vs -2.97 mm Hg; P < .001) and diastolic (-2.92 vs -2.48 mm Hg; P = .01) blood pressure, and levels of high-density lipoprotein cholesterol (3.67 vs 1.97 mg/dL; P < .001) and triglycerides (-25.56 vs -19.75 mg/dL; P < .001). Reductions in low-density lipoprotein cholesterol levels were greater in DSE than ILI participants (-11.27 vs -12.84 mg/dL; P = .009) owing to greater use of medications to lower lipid levels in the DSE group. At 4 years, ILI participants maintained greater improvements than DSE participants in weight, fitness, hemoglobin A(1c) levels, systolic blood pressure, and high-density lipoprotein cholesterol levels. Conclusions: Intensive lifestyle intervention can produce sustained weight loss and improvements in fitness, glycemic control, and CVD risk factors in individuals with type 2 diabetes. Whether these differences in risk factors translate to reduction in CVD events will ultimately be addressed by the Look AHEAD trial. Trial registration: clinicaltrials.gov Identifier: NCT00017953.