VOLUME 11 NUMBER 2 • JUNE 2014
87
SA JOURNAL OF DIABETES & VASCULAR DISEASE
REVIEW
Correspondence to: Oliver Schnell
Forschergruppe Diabetes e.V., Helmholtz Center Munich, Munich-
Neuherberg, Germany
e-mail:
Eberhard Standl
Forschergruppe Diabetes e.V., Helmholtz Center Munich, Munich-
Neuherberg, Germany
Francesco Cappuccio
University of Warwick, Warwick, UK
Stefano Genovese
Department of Cardiovascular and Metabolic Diseases, Gruppo
Multimedica, Sesto San Giovanni, Milan, Italy
Paul Valensi
Service d’Endocrinologie-Diabétologie-Nutrition, Hôpital Jean Verdier,
Bondy Cedex, France
Antonio Ceriello
Insititut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) and
Centro de Investigación Biomédica en Red de Diabetes y Enfermedades
Metabólicas Asociadas (CIBERDEM), Hospital Clínic Barcelona, Barcelona,
Spain
Originally published in
Cardiovasc Diabetol
2013,
12
: 156.
S Afr J Diabetes Vasc Dis
2014;
11
: 87–94
Type 1 diabetes and cardiovascular disease
OLIVER SCHNELL, FRANCESCO CAPPUCCIO, STEFANO GENOVESE, EBERHARD STANDL, PAUL
VALENSI, ANTONIO CERIELLO
Abstract
The presence of cardiovascular disease (CVD) in type 1
diabetes largely impairs life expectancy. Hyperglycaemia,
leading to an increase in oxidative stress, is considered to
be the key pathophysiological factor of both micro- and
macrovascular complications. In type 1 diabetes, the presence
of coronary calcifications is also related to coronary artery
disease. Cardiac autonomic neuropathy, which significantly
impairs myocardial function and blood flow, also enhances
cardiac abnormalities. Also hypoglycaemic episodes are
considered to adversely influence cardiac performance.
Intensive insulin therapy has been demonstrated to
reduce the occurrence and progression of both micro- and
macrovascular complications. This has been evidenced
by the Diabetes Control and Complications Trial (DCCT)/
Epidemiology of Diabetes Interventions and Complications
(EDIC) study. The concept of a metabolic memory emerged
based on the results of the study, which established that
intensified insulin therapy is the standard of treatment of
type 1 diabetes. Future therapies may also include glucagon-
like peptide (GLP)-based treatment therapies. Pilot studies
with GLP-1-analogues have been shown to reduce insulin
requirements.
Keywords:
type 1 diabetes, cardiovascular disease
Introduction
Over the past 40 years, a reduction in mortality rate due to
cardiovascular disease (CVD) and coronary heart disease (CHD) by
about 70%, both in diabetic and non-diabetic patients, has been
observed.
1
The cause is presumed to be a substantial progress in CV
risk factor management and interventional cardiology.
1
Furthermore,
in patients with type 1 diabetes, a decrease in mortality and a
remarkable improvement in life expectancy has occurred during the
past decades.
2,3
The comparison of two sub-cohorts of the Pittsburgh
Epidemiology of Diabetes Complications (EDC) study based on the
period of diabetes diagnosis (1950–1964 vs 1965–1980) found an
increase in life expectancy of approximately 14 years.
3
Nevertheless,
the overall risk of CVD for people with type 1 diabetes compared
to people without diabetes is increased two- to three-fold in men,
and three- to five-fold in women. A significant increase in CVD
mortality related to increasing glycated haemoglobin (HbA
1c
) levels
has been reported in type 1 diabetes.
4
The aim of this article was to present an overview on
epidemiological and pathophysiological aspects of the relationship
between type 1 diabetes and CVD. In addition, the management
of risk factors, both with a view on diagnostic and therapeutic
approaches, is addressed.
Epidemiology
In the EURODIAB IDDM Complications study, including more than
3 200 patients with type 1 diabetes from 16 European countries,
the prevalence of CVD was reported to be 9% in men and 10% in
women, respectively.
5
Related to an increase in duration of diabetes
and age, an increase from 6% in the age group of 15–29 years to
25% in the age group of 45–59 years, has been observed.
5
In type 1 diabetes compared to type 2 diabetes, the relationship of
hyperglycaemia with microangiopathy as well as macroangiopathy
seemed to be more significant.
6,7
According to the results of a large
Finnish database, CVD mortality in patients with type 1 diabetes
aged from 45–64 years at baseline increased by about 50% with
every 1% increase in HbA
1c
level.
6
In a population-based cohort of 879 individuals with type 1
diabetes from Wisconsin, hyperglycaemia was associated with all-
cause and cardiovascular mortality.
8
At baseline examination (1980–
1982), patients were free of cardiovascular disease and end-stage
renal disease. The patients were followed up until December 2001.
The multivariable relative risks comparing the highest quartile of
HbA
1c
(≥ 12.1%) with the lowest quartile (≤ 9.4%) were 2.42 (95%
CI: 1.54–3.82;
p
=0.0006) for all-cause mortality and 3.28 (95% CI:
1.77–6.08;
p
<0.0001) for cardiovascular mortality.
8
This association
was present among both sexes, and independent of duration of
diabetes, smoking, hypertension and proteinuria. The relationship
persisted in subgroup analyses by categories of diabetes duration,
smoking, body mass index, proteinuria and retinopathy.
8
In a Japanese study, which included type 1 diabetes subjects
who were diagnosed at an age of < 18 years, between 1965 and
1979, CVD was identified as the leading cause of death in diabetes
of more than 20 years of duration.
9
Recently, the long-term clinical outcomes and survival in patients
with both young-onset type 2 and type 1 diabetes with a similar
age of diagnosis were evaluated.
10
Compared with type 1, type
