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Current Vascular Pharmacology, 2020, 18, 104-109

REVIEW ARTICLE
ISSN: 1570-1611
eISSN: 1875-6212

Current Vascular
Pharmacology
The journal for current and in-depth reviews on Vascular Pharmacology

The Growing Epidemic of Diabetes Mellitus Impact

Factor:
2.58

BENTHAM
SCIENCE

Dragan Lovic1,*, Alexia Piperidou2, Ioanna Zografou2, Haralambos Grassos3, Andreas Pittaras4 and
Athanasios Manolis4

1
Clinic for Internal Disease Intermedica, Nis, Serbia; 22nd Propedeutic Department of Internal Medicine, Aristotle
University, Thessaloniki, Greece; 3Cardiology Department, KAT Hospital, Athens, Greece; 4Cardiology Department,
Asklepeion Hospital, Athens, Greece

Abstract: Background: During the past decades, the prevalence of diabetes (DM) has increased signifi-
cantly, mainly as a result of continuous rise in the incidence of type 2 DM. According to World Health
Organization statistics, >422 million adults globally were suffering from DM in 2014 and a continuous
rise in DM prevalence is expected.
Objective: The present review considers recent epidemiological data providing worldwide estimates
regarding the incidence of DM.
ARTICLE HISTORY
Methods: A comprehensive literature search was conducted to identify available data from epidemiol-
ogical studies evaluating the current burden of DM.
Current Vascular Pharmacology

Received: October 22, 2018

Revised: December 11, 2018 Results: Over the past few decades the prevalence of DM has risen significantly in nearly all countries
Accepted: December 17, 2018
and may be considered as a growing epidemic. Urbanization and income status are major factors which
DOI: influence current rates in the prevalence studies introducing interesting differences between several
10.2174/1570161117666190405165911
population groups.
Conclusion: Having recognized the global burden of DM, we now realize the urgent need for effective
interventions. In order to monitor the public-health strategies and design effective future interventions
we need reliable global estimates regarding the prevalence of DM.
Keywords: Diabetes mellitus, type 1 diabetes, type 2 diabetes, gestational diabetes, impaired glucose tolerance, impaired fast-
ing glycaemia, prevalence, incidence, epidemiology.

1. INTRODUCTION environmental and genetic factors interact for the develop-

Diabetes mellitus (DM) is a chronic metabolic disorder
characterized by elevated levels of plasma glucose. Concern-
ing the pathogenesis of the disease, two major mechanisms
have been proposed. Autoimmune destruction of the pancre-
atic β- cells with consequent insufficient insulin production
as well as endogenous resistance of the body cells to insulin
action are the leading causes for chronic hyperglycaemia
associated with DM [1].
There are 3 main types of DM: type 1 DM (T1DM), type
2 DM (T2DM) and gestational DM (GDM). The first type,
also known as “juvenile/childhood-onset diabetes” or “insu-
lin-dependent diabetes” is defined by the deficiency of insu-
lin production in human body and its treatment requires
regular administration of insulin analogues [2, 3]. The exact
cause of T1DM is not yet discovered. However, it is gener-
ally agreed by the scientific society that a complex of
*Address correspondence to this author at the Clinic for Internal Disease
Intermedica, Hypertension Centre, Jovana Ristica str. 20-2, 18000 Nis,
Mediana, Serbia; E-mail: draganl1@sbb.rs
ment of T1DM at its early stages [4]. T2DM which was for-
merly called “adult-onset diabetes” or “non-insulin-
dependent diabetes”, is characterized by insulin resistance
[2, 4]. In other words, it is the result of ineffective response
of the body to the produced insulin. As the disease pro-
gresses, insulin deficiency may also occur. Ethnicity, family
history of DM combined with obesity, unhealthy dietary and
limited physical exercise are the primary causes of T2DM [3,
4]. The grey zone of the transition from normoglycaemia to
DM is often characterized as “Impaired Glucose Tolerance”
(IGT) or “Impaired Fasting Glycaemia” (IFG). The last 2
conditions are generally recognized as precursors of T2DM,
since it is estimated that about 1 out of 4 individuals with
IGT/IFG will progress to DM within a period of 3-5 years
[5]. Finally, gestational DM is the condition of elevated
blood glucose during pregnancy in women without a previ-
ous history of DM [2]. In this case the infant is at high risk
of developing DM later in their adulthood.
DM is an important public health issue, recognized as
one of the most common chronic diseases in nearly all coun-

1875-6212/20 $65.00+.00 © 2020 Bentham Science Publishers

The Rising Prevalence of Diabetes
tries; associated with premature death and disability [4]. Ac-
cording to the American Diabetes Association (ADA) esti-
mates, the national costs for all cases of diagnosed DM in the
USA for 2012 were about $245 billion, while the average
medical costs for patients with DM were $12,700 annually
[6]. Chronic hyperglycaemia due to DM is followed by sev-
eral macrovascular (ischaemic heart disease, stroke and pe-
ripheral artery disease) and microvascular (neuropathy,
nephropathy and retinopathy) complications. Glucose-
lowering strategies, aiming to a better control of DM meta-
bolic disorders as well as lifestyle changing campaigns are
needed to reduce the incidence of the previously mentioned
manifestations. However, long-term optimal glycaemic con-
trol is not always achieved in these patients [7].
In order to improve our therapeutic goals and reduce cur-
rent rates of morbidity and mortality associated with DM we
should firstly understand in depth the burden of the disease.
During the past decades, the prevalence of DM increased
dramatically, mainly as a result of continuous rise in the in-
cidence of T2DM [8]. According to World Health Organiza-
tion (WHO) statistics >422 million adults globally were suf-
fering from DM in 2014 [9]. A continuous rise in DM preva-
lence is expected. The International Diabetes Federation
(IDF) predicts that this number will rise to 642 million by
2040 [10]. The present review considers the recent epidemi-
ological data providing worldwide estimates regarding the
incidence of DM.
2. PREVALENCE OF DM
Recent findings suggest that the burden of DM has risen
significantly over the past decade and may be considered as
a growing epidemic. In greater detail, 8.8% of the adult
population is diagnosed with DM [10]. If these trends are not
reversed, it is predicted that by 2040 about 693 million indi-
viduals aged 18-99 years, which represents 9.9% of the
world’s population, will have DM [10].
2.1. Incidence of People with DM by Type of Diabetes
In 2017 approximately 8.8% of the world’s adult popula-
tion suffered from DM; a percentage which represents 424.9
million individuals according to that year’s estimates and is
greater than the estimated number which was published ear-
lier by the WHO in 2014 [4, 10]. According to IDF esti-
mates, by 2045, an increase of 1.1% in the prevalence of DM
is expected. Furthermore, the number of patients with T1DM
aged 0-19 years is currently 1,105,500 million, whereas the
cases of newly diagnosed children and young adolescents are
132,600 [10]. The annual increase in this category is esti-
mated approximately 3% [11-13]. About T2DM, which is
often undiagnosed, studies evaluating the number of newly
diagnosed cases are complicated and as a result there are
almost no reports on true prevalence [4]. Regarding IGT,
current statistics reveal that there are 352.1 million patients
worldwide, and it is projected that the total number of people
20-79 years old with IGT will rise to 587 million in the fu-
ture [10]. Finally, hyperglycaemia in pregnancy was ob-
served in 21.3 million of live births in 2017; the majority of
the cases (86.4%) were due to GDM affecting mainly the age
group 40-49 years, whereas the remaining ones were related
to other types of DM [10]. Due to significant variations
Current Vascular Pharmacology, 2020, Vol. 18, No. 2 105
among recent data for GDM prevalence, future projections of
the increase rate are insecure [14].
2.2. Incidence of DM by Region
Prevalence rates of DM differ among several regions
[15]. According to the IDF estimates, the North American
and Caribbean region has the highest incidence rates reach-
ing 13% of the total population in 2017, a percentage which
is expected to rise up to 14.8% by year 2045 [10]. More spe-
cifically, in the United States 30.2 million people aged 20-79
years were suffering from DM in 2017. Lower but still sig-
nificant rates were observed in countries of the Middle East
region. In 2013, there were approximately 34.6 million pa-
tients with DM [16], while in 2017 the same estimation rose
to 39 million [10]. In China and India, DM was diagnosed in
114.4 and 72.9 million adults, respectively. Until 2035, a
96% increase in the incidence of the disease is predicted in
these countries [16]. Regarding Europe, epidemiological
studies show that the prevalence rates are lower compared
with the countries already described. Current data support
that approximately 8.8% of Europe’s adult population is suf-
fering from DM and it is estimated that in the following 3
decades it will rise to 10.2% [10]. In other words, according
to recent study data in year 2035 there will be about 68.9
million adults with DM in Europe [16]. On the other hand,
the lowest prevalence of DM is recorded in the Africa re-
gion, which was 4.4% in 2017 [10]. Lower rates of urbaniza-
tion, undernutrition as well as lower Body Mass Index (BMI)
levels are the main reasons for the previous regional dispari-
ties [17]. Nevertheless, future increase in this region’s esti-
mates is also described [15, 16].
2.3. Incidence of People with DM by Age and Sex
The prevalence of DM increases significantly with age
[9, 18]. The majority of diagnosed cases lie between the
fourth and seventh decade of life [10]. According to the most
recent data, >326 million people of working age suffer from
DM in contrast to 122.8 million aged over 65 years [10].
These numbers are expected to rise up to 438.2 million and
253.4 million, respectively in the upcoming decades [10].
Moreover, the incidence of T1DM is typically higher in the
first decades of life; between birth and 14 years [19]. How-
ever, this conclusion might be influenced by the fact that
there are no published population-based incidence data for
greater ages. Much of our knowledge on the subject has been
generated by international standardized registries of new
cases such as the WHO DIAMOND Project [4, 13]. Accord-
ing to this, there is a wide diversity in the prevalence rates of
T1DM in children under 15 years, ranging from 0.5 to over
60 cases per 100,000 patients annually. Regarding gender
distribution, there is a slight trend in the male population. In
2017, the cases of DM diagnosed in women aged 20-79
years were 8.4% compared with 9.1% observed among men;
a difference which will be significantly reduced in future
times, since it is expected that the above percentages will rise
to 9.7% and 10%, respectively [10].
2.4. Rural and Urban Environments, Income Status
Urbanization has significantly affected current trends in
the incidence of DM [20]. In 2017, the number of adult pa-
106 Current Vascular Pharmacology, 2020, Vol. 18, No. 2
tients were 279.2 million in urban centres compared with
145.7 million in rural settings [10, 21]. Interesting differ-
ences in the incidence rates exist, also, between several
country income groups. According to Dagenais et al. the
frequency of DM cases in a multivariable analysis after ad-
justments for age and sex was higher in low-income coun-
tries (Bangladesh, India, Pakistan and Zimbabwe) (12.3%,
95%CI 10.9-13.9%), followed by upper middle-income (Ar-
gentina, Brazil, Chile, Malaysia, Poland, South Africa and
Turkey) (11.1%, 95%CI 9.7-12.6%) and lower middle- in-
come (China, Colombia, Iran, and Palestine) (8.7%, 95%CI
7.9-9.6%). The lowest prevalence was observed in high in-
come countries (Canada, Sweden, and the United Arab Emir-
ates), (6.6%, 95%CI 5.7-7.7%) [22]. Low education level,
rapid industrialization, unhealthy lifestyle changes including
tobacco consumption, limited physical activity and calorie-
dense diets might partially explain the previous trends no-
ticed in developing versus developed countries.
3. CONTRIBUTING FACTORS
Even though the exact causes of T1DM are not yet clari-
fied, the possible genetic component of the disease has been
strongly supported in the literature [23]. However, the het-
erogeneity of “juvenile diabetes” cannot be adequately ex-
plained only by the presence of specific genetic patterns
[24]. Thus, the theory of an interplay between environmental
and genetic factors has been proposed. According to recent
study data, dietary habits such as elevated intake of complex
dietary proteins, fetal and perinatal factors, such as rapid
weight gain during childhood, maternal age and birth weight
as well as exposure to several pathogens have been shown to
play significant role in the incidence of T1DM through cer-
tain pathogenetic mechanisms [25-28].
The development of T2DM is highly associated with a
variety of modifiable and non-modifiable risk factors [15].
Among them, overweight (BMI ≥25 kg/m2) and obesity
(BMI ≥30kg/m2) are the most potent [17]. Moreover, limited
physical activity, sedentary behaviour, certain dietary habits
including high-calorie intake and cigarette smoking contrib-
ute to the currently elevated prevalence rates of T2DM [29,
30]. On the other hand, increasing age, male sex as well as
family history of DM are important non-modifiable risk fac-
tors for DM [15]. There is also evidence that women with
GDM are exposed to higher risk (about 7-fold) of presenting
with T2DM later in life compared with women with normo-
glycaemic pregnancy [31]. Apart from the risk factors al-
ready described, genome-wide association analyses have
recently proposed the possible relationship of certain genetic
variants with the progression to DM [32, 33]. Future studies
in the field are required in order to enlighten the pathophysi-
ological pathways through which these genetic variants lead
to hyperglycaemia.
4. WHAT TO DO TO DECREASE THE RISK OF DE-
VELOPING DM?
4.1. Primary Prevention
Management of DM across decades has been a great
challenge to healthcare professionals as a consequence of its
increasing prevalence and numerous complications. Primary
prevention is essential. Regarding T1DM, intervention
Lovic et al.
strategies and prevention programs have not been successful
yet, due to inability of the current data to identify the leading
causes and risk factors of the disease [10].
Therefore, this paragraph focuses mainly on measures
that have been proposed for the prevention of T2DM. High
quality of evidence from the Diabetes Prevention Program
(DPP) supports the beneficial effects of DM prevention. The
DPP showed that intensive lifestyle modifications could re-
duce the prevalence of T2DM by about 60% over 3 years of
follow-up [34]. In particular, interventions aiming at a
healthy diet with a low-calorie eating pattern, increased
physical activity and the reduction in alcohol and tobacco
consumption are expected to prevent or at least delay the
onset of DM. The potential role of several pharmacologic
agents in the prevention of DM has also been investigated.
Metformin administration demonstrated long-term efficacy
and safety when used as a measure for T2DM. However,
when compared with lifestyle modification, no other inter-
vention showed the same beneficial outcomes [35, 36].
What still needs to be determined is how individuals at
high risk who would benefit from such interventions, will be
identified [15, 16, 19]. According to the ADA, HbA1c levels
should be the criterion. More specifically, persons with an
HbA1c 5.7- 6.4% should be considered at high risk of devel-
oping DM; thus, lifestyle and pharmacological interventions
are required [2]. However, the above criterion reduces sig-
nificantly the total amount of people who would be other-
wise identified to be at high risk for presenting hypergly-
caemia based on traditional glucose measurements [37-39].
On the other hand, no similar HbA1c threshold has been
proposed by the WHO for the detection of intermediate hy-
perglycaemia [37].
Furthermore, evidence from clinical trials show that this
1-dimensional approach, which only addresses high-risk
individuals might not be the most effective strategy in the
real-world setting [19]. Although people participating in
these programs may benefit significantly, there is limited
impact on the public health prevalence of DM. Conse-
quently, multi-pronged approaches aiming to a better control
of the modifiable risk factors such as diet and physical activ-
ity in the population- and not individual-level might have
great impact on the public health burden of DM [40]. Find-
ing ways of combining high risk and population approaches
in prevention strategies as well as balancing the relative ef-
fort in these is a future challenge [19]. Finally, GDM should
also be included in the previous actions, since it has a major
impact on the DM burden. Measures that not only promote
better management of glucose intolerance during pregnancy
but also ensure educational purposes in order to avoid poten-
tial risks (behavioural and environmental) are required [16].
4.2. Managing DM
The combination of pharmacologic and non-
pharmacologic interventions, which aim to control blood
glucose levels and cardiovascular disease risk is considered
to be the “best practice” in the management of DM. Early
detection of clinical symptoms and diagnosis of DM are con-
sidered to be fundamental for the long-term control of the
disease and its complications which have direct impact on
the individual’s quality of life [41]. Additional investment is
The Rising Prevalence of Diabetes
required for the development of screening programs that will
increase the number of clinically diagnosed cases of DM and
consequently the health-care system workload. According to
guidelines developed by the ADA and management proto-
cols published by the WHO, the therapeutic approach of pa-
tients with DM should be systematically delivered by a team
of skilled professionals and should include intensive lifestyle
modifications, medication for blood glucose lowering, treat-
ment of cardiovascular risk factors, as well as regular exami-
nation for early diagnosis of the disease’s complications [2,
4].
More detailed, lifestyle interventions, such as those de-
scribed in the previous section, focus mainly on the reduc-
tion of saturated fat intake, weight loss when indicated, in-
creased physical activity and the avoidance of alcohol and
tobacco consumption [42-44]. Regarding pharmacologic
treatment, there are several therapeutic choices including
antihyperglycaemic medicines and insulin analogues, which
are used according to the specific type of DM; the majority
of patients with T1DM are treated with multiple daily injec-
tions of short acting and basal insulin, while in T2DM either
monotherapy or combination therapy of drugs and/or insulin
analogues is administered [45, 46]. Treatment goals should
be monitored through regular blood glucose measurements.
Furthermore, comprehensive reduction of macrovascular and
microvascular complications associated with DM is required.
Intensive control of blood pressure and lipid management are
of vital importance in the prevention of cardiovascular dis-
ease [47-50]. Retinopathy, nephropathy and neuropathy can
be slowed or even prevented through screening tests and
appropriate medication [2, 4].
All in all, the effectiveness of the above interventions
which are aimed at better management of DM, ultimately
depends on patient compliance with the provided recom-
mendations. The reorientation of healthcare systems towards
the expansion of universal health coverage providing the
access of all people to essential medicines, will improve our
attempts to manage the burden of DM and its lifelong co-
morbidities [51].
5. DISADVANTAGES OF PREVALENCE RATES
As the prevalence of DM continues to rise, the need for
valid global estimates becomes more urgent [16]. Accurate
data of the incidence rates are required not only for maintain-
ing public awareness on the burden of DM but also for opti-
mizing management interventions [52]. They are important
for directing the actions of the health-care systems and iden-
tifying subgroups of patients with specific characteristics that
might be benefited by special handling. Apart from improv-
ing our treatment strategies, reliable data are also valuable in
monitoring the effectiveness of the above, and consequently
reorienting them according to future trends [53].
However, the integrity of current statistics has been ques-
tioned. First of all, the lack of a uniform standardized proto-
col has a major impact on the comparability of the data [9].
There is a wide variety of methods and criteria which are
used in the prevalence studies for the diagnosis of DM. This
introduces methodological differences between the analyses,
and thus any comparison is insecure and fraught with diffi-
culty. Additionally, there are several limitations concerning
Current Vascular Pharmacology, 2020, Vol. 18, No. 2 107
specific diagnostic methods. The majority of the epidemiol-
ogical studies use fasting plasma glucose for the identifica-
tion of patients with DM. However, this method significantly
underestimates the incidence of the disease. Moreover, the
criteria which are used in most of these studies for the diag-
nosis of the several types of DM cast serious doubts about
the integrity of their estimations. Traditionally, the preva-
lence of T1DM in children and young adults is recognized
within registries of newly diagnosed DM as all cases of pa-
tients that require daily administration of insulin analogues
[54, 55]. As a result of the previous assumption, almost all
cases of DM in paediatric population are determined as
T1DM. The latter produces insecure results, since some
forms of T2DM, which according to recent data are also in-
creasingly being recognized in childhood and adolescence
(such as maturity- onset diabetes- MOD), are not recorded
[56-58]. Similarly, in the prevalence studies almost all cases
of adult patients with DM are considered to have T2DM;
thus, some forms of T1DM which are characterized by later
onset during adulthood escape detection [54, 55, 59]. In
other words, current estimates regarding clinically diagnosed
T1DM and T2DM may be considered as only rough esti-
mates.
Apart from the lack of uniform standards in data report-
ing, another major issue in obtaining accurate estimates
about the global burden of DM is that there are very few data
regarding developing countries [53]. According to a recent
study by Makaroff et al., high-quality prevalence data is
available only for the percentage of 57% of a total of 221
countries and territories [60]. In order to overcome this prob-
lem, many organizations (such as the IDF) that play an im-
portant role in the field of DM through their actions, decided
to extrapolate data from other nations with similar demo-
graphic characteristics in cases of countries without national
data on the incidence of DM [10]. However, the methodo-
logical accuracy of this technique cannot be guaranteed. Its
basis on similar features between nations is very fragile and
can be easily questioned at a social, economic and ethnic
level.
Taking into consideration all the above limitations of the
epidemiological studies it can be concluded that only broad
estimations can be drawn by their data. Attempts that aim to
improve the process of obtaining reliable data should be
strongly encouraged.
CONCLUSION
Over the past few decades the prevalence of DM has
risen significantly in nearly all countries becoming a “grow-
ing epidemic”. Urbanization which is a trend affecting al-
most all nations, has a major impact on the incidence of DM.
According to the most recently published data, the total
number of adult patients in urban centres is twice as high
than in rural settings. Income status is another factor which
influences current rates in the prevalence studies introducing
interesting differences between several country income
groups. Low education level, rapid industrialization, un-
healthy lifestyle, which are all characteristics of the low-
income countries, can explain the significantly higher rates
of DM recorded in these regions.
108 Current Vascular Pharmacology, 2020, Vol. 18, No. 2 Lovic et al.

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