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Epidemiology of Type 1 Diabetes in Latin America

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Current Diabetes Reviews, 2014, 10, 61-73 1

Epidemiology of Type 1 Diabetes in Latin America

Rita Angélica Gómez-Díaz1,*, Nayely Garibay-Nieto2, Niels Wacher-Rodarte1 and Carlos Alberto
Aguilar-Salinas3,*

1
Unidad de Investigación Médica en Epidemiología Clínica. UMAE Hospital de Especialidades. Centro Médico
Nacional “Siglo XXI”. Instituto Mexicano del Seguro Social. México City, Mexico; 2 Clínica de Obesidad Infantil.
Hospital General de México. México City, Mexico; 3Departmento de Endocrinología y Metabolismo, Instituto Nacional
de Ciencias Médicas y Nutrición. México City, Mexico

Abstract: Latin America is among the regions with the highest diabetes-related burden. Research and treatment programs
have increased in number and complexity in recent years, but they are focused in type 2 diabetes, because this condition
explains a large proportion of the cases. In contrast, the information regarding the epidemiology of type 1 diabetes is scant
in this area. Here, we analyze the available information on this topic and identify potential areas of opportunity to generate
new knowledge through the study of type 1 diabetes in Latin Americans.
Both, the prevalence and the incidence of type 1 diabetes, are lower in Latin American countries compared to that re-
ported in Europe, North America, southern Asia and northern Africa. Biologic and methodological factors may explain
the smaller contribution of type 1. The presence of some putative 'protective' environmental exposures or the absence of
those prevalent in a region may explain the lower type 1 diabetes prevalence observed in most Latin American countries.
However, the number and quality of the diabetes registries are not enough in this region. During the past decade, the inci-
dence of type 1 diabetes has grown worldwide. The same trend has been reported in Latin America. This epidemiologic
transition is a unique opportunity to identify interactions between rapidly changing environmental factors in subjects with
different genetic backgrounds (such as the admixed Latin American populations). Finally, on-going therapeutic initiatives
in this region are highlighted.

Keywords: Incidence, type 1 diabetes, pediatric population, Latin America, diabetes costs, diabetes programs.

INTRODUCTION
Type 1 Diabetes (T1D) has been considered an autoim-
mune disease characterized by destruction of pancreatic insu-
lin secreting beta-cells. Pathogenesis is multifactorial and
caused by interaction of genetic, epigenetic and environ-
mental factors leading to early in life production of autoanti-
bodies that promote pancreatic chronic inflammation and
gradual loss of insulin secreting capacity [1]. Although T1D
can occur at any age, it has been predominantly described as
a childhood disease since more than 50% of people with
T1D are diagnosed before the age of 15. The peak onset in-
cidence is between 6 and 15 years of age and a second one is
observed later in adolescence. Nevertheless, life expectancy
and quality of life have significantly improved thanks to ef-
ficient insulin replacement therapy, mainly in the absence of
renal damage development [2].
Overall incidence and prevalence of type 1 and 2 diabetes
have increased during the last decades. The International
Diabetes Federation (IDF) reported in its 6th edition that 382
million people worldwide are affected by this disease, while
projections to 2035 predict that this will rise to 592 million.
According to the IDF, the incidence of type 1 diabetes
among children is increasing in many countries, particularly
in children under the age of 15 years. More than 79,000 chil-
dren developed T1D in 2013. Type 1 diabetes, although less
common than type 2 diabetes, is increasing each year in both
rich and poor countries. In most high-income countries, the
majority of diabetes in children and adolescents is caused by
T1D. Young people with T1D show an annual increase in
incidence of 3% and it is estimated that 497,100 children
under 15 years of age have T1D. Of them, 26% live in
Europe and 22% in North America and the Caribbean [3].
Nevertheless the global variation in the incidence has been
shown to be large. In general, the incidence increases with
age; the 5-9 year olds have 1.62 (1.57-1.66) times higher
risk, and the 10-14 year olds 1.94 (1.89-1.98) times higher
risk than that in the group 0-4 year olds and it is not gener-
ally influenced by gender [4].

WORLDWIDE INCIDENCE AND PREVALENCE OF

*Address correspondence to these authors at the Departamento de
Endocrinología y Metabolismo. Instituto Nacional de Ciencias Médicas y
Nutrición. Vasco de Quiroga 15. Mexico City 14000, Mexico; Tel: (52-55)
56554523; Fax: (52-55)55130002; E-mail: ---------------------- and Unidad
de Investigación Médica en Epidemiología Clínica, UMAE Hospital de
Especialidades, CMN-SXXI, IMSS Av. Cuauhtémoc #330, Col. Doctores,
Deleg. Cuauhtémoc, 06725 México, D.F., México; Tel: (52-55) 5627-6900
ext. 21481, 21507; E-mail: ritagomezdiaz@yahoo.com.mx
CHILDHOOD TYPE 1 DIABETES
The World Health Organization (WHO) coordinated a
Multinational Project for Childhood Diabetes (DIAMOND)
from 1990 to 1999 in order to monitor the patterns of
worldwide incidence of T1D in children up to the year 2000

1573-3998/14 $58.00+.00 © 2014 Bentham Science Publishers

2 Current Diabetes Reviews, 2014, Vol. 10, No. 2
[5]. Diabetes and Genetic Epidemiology Unit of the National
Public Health Institute in Helsinki, Finland served as the
coordinator unit and 100 centers from 50 countries around
the world headed by a principal investigator were recruited.
To be eligible, the center must have an accurate well-defined
population based registry. The inclusion criteria considered
children 0-14 years with residency in the study area. Fifty
countries participated in this program. Seventy-five million
children fitted inclusion criteria and 19,164 were diagnosed
with T1D from 1990 to 1994, according to WHO classifica-
tion and diagnostic criteria. Ten Latin American countries
(Argentina, Brazil, Chile, Colombia, Paraguay, Perú, Uru-
guay, Venezuela, Cuba and México) participated with 13
centers. The overall age-adjusted incidence of T1D varied
from 0.1/100,000/year in Zunyi, China and Venezuela, to
36.8/100,000 in Sardinia and 36.5/100,000 in Finland (350-
fold variation among 100 populations around the world).
Most of the populations in the Asian continent had a very
low (< 1 per 100,000/year) or low incidence (1-
4.99/100,000/year). Populations of the African continent had
intermediate incidence (5-9.99/100,000/year) One-half of
European countries exerted an intermediate incidence while
the rest had high rates (10-19.99/100,000/year) or very high
(
20/100,000/year). The incidence among populations in
South America ranged from intermediate to very low; in
Central America and the West Indies, Puerto Rico and Vir-
gin Islands incidence was high as well as in Oceania. In the
overall 1990-1999-period the incidence among South
American populations varied between very low to high. The
highest incidence rates were among European and North
American populations. A marked within-country variation in
the age-adjusted incidence in most of the countries with
more than one center was observed. The global incidence
trend during the 10-year observation period showed an aver-
age annual increase of 2.4% between 1990 and 1994 and
3.4% between 1995-1999, but the difference was not statisti-
cally significant [4]. The incidence increase was less in older
age groups, particularly in European populations.
Other registries were implemented in the United States of
America (U.S.) and in Europe. The Centers for Disease Con-
trol and Prevention (CDC) and the National Institute of Dia-
betes and Digestive and Kidney Diseases provide funds for
the SEARCH (Search for Diabetes in Youth) study, a multi-
center survey based in six centers that recollects information
of new cases with diabetes. The incidence rates were the
highest in Caucasians among ethnic groups. The SEARCH
registry has provided incidence rates by age and gender
groups in selected areas of Colorado, Ohio, South Carolina
and Washington, among health plan members of Kaiser
Permanente Southern California and among American Indi-
ans living on reservations in Arizona and New Mexico. In its
most recent report, the SEARCH study group informed the
results from a population of 3,458,974 youth aged < 20
years. The number of cases with diabetes included was 7,695
(incidence 2.22/1000). Of them, 6,668 had type 1 diabetes
(1.93/1000), 837 had type 2 (0.24/1000) and 190 (0.05/1000)
had other diabetes types. Prevalence increased with age, was
slightly higher in females than males, and was most preva-
lent in Caucasians and least prevalent in Asian/Pacific Is-
landers, with Native American and Black youth having the
highest prevalence of type 2 diabetes [6]. In Europe, the
Gómez-Díaz et al.
EURODIAB study has recollected the information of 23
centers that cover a geographically defined region. This sur-
vey has generated numerous reports. Two rounds of esti-
mates (1989-1998 and 1999-2008) of the incidence of type 1
diabetes were published recently [7]. This effort includes
49,969 new cases aged 15 or younger when diagnosed. The
incidence rates increased in both periods covered by the
study (3.4% per annum and 3.3% per annum in the first and
second period respectively). However, remarkable differ-
ences were found between centers. The authors concluded
that the incidence of type 1 diabetes is growing 3-4% per
annum, but this trend is not uniform.
Recently, the information provided by the 6th edition of
the International Diabetes Federation (IDF) Atlas about the
prevalence of type 1 diabetes in the young was extended by
Patterson et al [8]. The authors performed a systematic re-
view in bibliographic databases. They concluded that there is
a lack of information about the prevalence of type 1 diabetes;
the majority of the reports are limited to the description of
the incidence rates. Information was available for 88 of the
216 countries (41%). The estimated number of children with
type 1 diabetes was 497,100. The largest number of patients
(129,000) came from the Middle East/North Africa region,
followed by North America and the Caribbean (108,700),
South of Asia (77,900), Europe (64,300) and South America
(45,600). The smallest number was reported in the Western
Pacific (32,500). The number of cases was calculated for
each country using the 2012 United Nations population esti-
mates. The countries with largest number of cases were the
U.S. (85,600), India (67,700), Brazil (31,100), United King-
dom (19,200), Germany (16,500), Russia (16,000), Saudi
Arabia (14,900), Nigeria (13,400), México (13,400) and
Egypt (12,700). Regarding the incidence of T1D, the data
collected by Patterson is in agreement with the DIAMOND
report. The country with the biggest incidence rate (per
100,000 persons aged less than 15 years) is Finland (57.6)
followed by Sweden (43.1), Norway (32.8), Saudi Arabia
(31.4) and United Kingdom (28.2). In contrast, the countries
with the biggest number of new cases are the United States
of America, India, Brazil, United Kingdom and Russia.
Although a network of diabetes registries is the best
available option for describing the incidence and prevalence
of type 1 diabetes, the information described here clearly
reflects the limitations of this approach. The likelihood to
detect and include a case is heavily influenced by the exist-
ing medical infrastructure. Assuring the quality of the infor-
mation of the prevalent cases implies additional challenges.
As a result, epidemiological information about type 1 diabe-
tes should be carefully analyzed to detect bias. In addition,
there is a need for having continuous surveillance programs
capable to represent all ethnic groups and areas, regardless
its socioeconomic status.
TYPE 1 DIABETES INCIDENCE AND PREVALENCE
IN LATIN AMERICA
Latin America includes 21 countries and has a total popu-
lation of almost 600 million people. Social and economic
characteristics are shared between the countries of this area.
Ethnic diversity and the preservation of the Amerindian heri-
tage are unique features of the Latin American populations.
Type 1 Diabetes in Latin America Current Diabetes Reviews, 2014, Vol. 10, No. 2 3

Table 1. Incidence of Type 1 diabetes in Latin America per 100,000 population aged 14 years or younger.

Incidence (%) Annual Change of Estimate of

Country Study Period
(95% CI) Incidence Ascertainment (%)

Puerto Rico 1990-1999 16.8 (16.0-17.6) -1.0 (-2.7;0.7) 90-97

Uruguay (Montevideo) 1992 8.3 (5.4-11.7) * 97

Brazil (Sao Paolo) 1990-1992 8.0 (5.53-11.14) -16 (-48.6;37.2) 70-95

Argentina (Avellaneda) 1990-1996 6.3 (5.7-11.1) 0.4 (-8.8;10.5) 88-100

Argentina (Tierra de Fuego 1993-1996 10.3 (5.5-18.5) * 100

Colombia (Bogota) 1990 3.8 (2.9-4.9) *

97
Colombia (Cali) 1995-1999 0.5 (0.3-0.7) *

Chile (Santiago) 1990-1999 3.7 (3.4-4.0) 7.5 (4.3;10.9) 100

Cuba 1990-1999 2.3 (2.2-2.5) -10.8 (-13.4;-8.2) 25-100

Mexico (Veracruz) 1990-1993 1.5 (0.7-2.9) 100

Paraguay 1990-1999 0.9 (0.8-1.0) -0.5 (-5.7;4.9) *
Peru (Lima) 1990-1994 0.5 (0.4-0.64) 12.1 (-7.5;35.8) *
Republica Dominicana 1995-1999 0.5 (0.4-0.7) 12.6 (-11.4;43.0) *
Venezuela (Caracas) 1990-1994 0.1 (0.1-0.2) -6.8 (-24.6;15.3) *
Hispanics in USA 1990-1999 11.4 (10.1-12.9) 51-100

* Missing data
Adapted from The DIAMOND Project Group [4].

Meanwhile, the Amerindian component is the dominant ge-
netic background in Peru and Guatemala, its contribution is
minimal in areas of Argentina or Uruguay. In urban areas of
Colombia and México, the average proportion of Native
American and European admixture are 50-60% and 30-45%
respectively.
The Latin American health systems face a double chal-
lenge: a rapidly growing number of cases with chronic dis-
ease and the persistence of infectious conditions. Type 2
diabetes is a major cause of mortality and disability. The IDF
estimated that the age-adjusted prevalence for the region was
9.2% for adults (aged 20 to 79 years) in 2011. Only North
America (10.5%) and Southern Asia (10.9%) had a greater
prevalence of diabetes than Latin America. Two of the ten
leading countries for the number of cases are located in the
region (Brazil and Mexico). Twelve Latin American coun-
tries have prevalence higher than the world average (8.3%).
In addition, the increment in the number of cases is expected
to be greater in this region compared to other areas. As a
result, type 2 diabetes is among the health priorities of the
region.
In contrast to the wide spread perception about the grow-
ing impact of type 2 diabetes in Latin America, the informa-
tion about the epidemiology of type 1 diabetes in this region
is scant. The incidence of T1D in children aged 14 or
younger in selected areas of Latin America is shown in Table
1. The information comes mainly from local registries. Ten
Latin American countries participated in the DIAMOND
registry. These rates are lower than those described in Spain
(12.4/100,000 (11.7-13.1)) or Portugal 14.6/100,000 (10.6-
19.6), suggesting that the Amerindian genetic background
might be protective against T1D development. Native un-
mixed minority groups remain in rural areas of Mexico, Bo-
livia, Peru and Guatemala and they report a very low inci-
dence of T1D. Furthermore, diabetes prevalence seems to be
related to the proportion of Caucasoid populations in a cer-
tain country [9]. As recognized by the Diabetes Epidemiol-
ogy Research International Group, the ethnic diversity of the
Latin American populations yields an opportunity to identify
the existence of protective genotypes or the absence of sus-
ceptibility variants in the Amerindians [10].
As described in detail below, there is insufficient infor-
mation about the prevalence of T1D in the region. Reports
are limited to incidence rates in centers that are the main
provider of services for patients with diabetes in a defined
region. Furthermore, secular trends of the incidence of the
disease have been recorded in few studies. Other topics in
which additional studies are needed are the evaluation of the
contribution of type 2 diabetes using structured protocols,
the incidence of T1D in adults and population-based and
standardized diabetes registries designed to have nationwide
representativeness.
Chile
Between 1980 and 1993 a study conducted in native abo-
riginal Mapuche population from Chile showed a very low
incidence (0.43/100,000/year CI [0-0.95]) of T1D in children
under the age of 14. These data were significantly different
from that reported for Caucasian Chilean population in the
same study (1.58/100,000 CI [1.11-2.04] p<0.0016)) Even
4 Current Diabetes Reviews, 2014, Vol. 10, No. 2
though Caucasian heritage came mainly from Spain, inci-
dence of T1D in this Chilean subgroup was 7 times lower
than that reported for Madrid or Catalonia [11]. Another
Chilean study conducted in the urban area of Santiago in a
period of 18 years (1986-2003) reported an overall incidence
rate of 4.02 (CI 2.98-4.83). Nevertheless, incidence showed
a growing trend that was more evident among boys [12].
Recent studies have evidenced the same phenomenon in an
urban population of Santiago that included subjects less than
15 years of age. A significant incidence increment was ob-
served in the period 2001-2004 (5.4 vs 8.33/100,000 inhabi-
tants/year, p<0.04). Higher rates were observed in the higher
income strata, urbanized counties and those with low Amer-
indian admixture [13]. Temporal patterns and interaction
with environmental factors were postulated as potential ex-
planations for the change in the incidence [14].
Uruguay
The Uruguayan population is a melting of Caucasian
(Spain, Italy, France, Portugal and Lebanon), Negroid
(Congo and Angola) and Amerindian (mainly Charrúas,
Minuanes and Garanies) groups. Intense admixture occurred
since the 17th and 18th centuries and it is impossible nowa-
days to find native unmixed ethnic groups, usually seen in
other countries of Latin America [15]. Interestingly, 92% of
the population in Montevideo is of Caucasian origin and it
represents one of the cities with the highest T1D incidence
according to the DIAMOND study in Latin America: 8.3%
(CI 5.4-11.7).
Mexico
Limited information regarding T1D incidence has been
published in Mexico. Data collected between 1978-1992
revealed a low incidence that was consistent with that issued
by the DIAMOND project group [16,4]. The study was con-
ducted under standardized methodology proposed by the
WHO in an urban area, Boca del Rio, a port located on the
Gulf of Mexico between 1990-1993. The average incidence
rate was 1.15/100,000/year (CI 0.75-1.9). These results have
positioned Mexico as the country with the lowest rates of
T1D incidence. Nevertheless, Gómez-Díaz and coworkers
recently reported remarkably greater incidence rates using as
source of documentation the database registries of the “Insti-
tuto Mexicano del Seguro Social”, the largest social health
care provider throughout the country [17]. Incidence among
children
19 years of age was calculated for a 10-year pe-
riod (2000-2010). The number of new cases with T1D in-
creased from 3.4 to 6.2 per 100,000 insured cases during the
study. The highest rate of new cases was seen in 2006, with
1,029 new cases in a population of 11,739,112 (8.8 new
cases/100,000 insured pediatric subjects). The age groups
with the biggest increment in number of cases were the 10-
14 years old (2.1-fold increase between 2003 and 2010) and
15-19 years old (1.9-fold increase between 2003 and 2010).
This study evidenced a substantial upward trend in T1D in-
cidence in Mexican children under 19 years. Even though
causative factors such as perinatal infections, weight increase
in the first months of life and increased maternal age might
be related to the outcome, it must be considered that inclu-
sion criteria were different for both studies.
Gómez-Díaz et al.
Argentina
Four Argentinean centers were included in the DIA-
MOND project. Avellaneda was the most representative city
of Caucasian population. Data were obtained from a retro-
spective study conducted from 1985 to 1988 (obtained from
the National Census). In addition prospective survey was
conducted from 1988 to 1994; the primary sources were pre-
primary and primary schools and secondary sources consid-
ered pediatric hospitals, private diabetologists and pediatri-
cians in Avellaneda, its surroundings and Buenos Aires city.
An annual incidence rate ranging from 6.89/100,000 year (CI
4.38-9.4) in 1985 to 7.59/100,000/year (CI 6.41-8.77) in
1990 was observed [18,4].
Hispanics Living in USA
Since 1980, the U.S. Hispanic population has grown from
14.6 million people, to nearly 53 million as of 2013, repre-
senting 17% of the overall American population (Census
Bureau 2013). As a result, Hispanics has become the first
minority group. Sixty-five percent of the US Hispanics has a
Mexican background. Other sources are Puerto Rico (9.4%),
El Salvador (3.8%), Cuba (3.6%), Dominican Republic (3%)
and Guatemala (2.3%). Arizona, California, Colorado, Flor-
ida, Illinois, New Jersey, New York and Texas all have a
population of 1 million or more of Hispanic residents. Cali-
fornia has the highest number of Hispanics of any state (14.5
million).
There are scant data about the prevalence of T1D in the
US. Orchard and coworkers applied two diagnostic criteria
in the NHANES 1999-2010 sample (n=59,130). The popula-
tion-based design of the survey and the small number of
cases limit the ability of the authors to provide precise esti-
mates of the prevalence. Regardless which criterion was ap-
plied the Hispanic population had half the prevalence of that
reported in Caucasians and African Americans. The same
conclusion was reached when the Mexican American sub-
jects was analyzed as a separate group [19].
The T1D incidence has been compared in US samples
between groups with different ethnic backgrounds. One of
the first studies reporting incidence was published in 1985
and was conducted in southern California between 1978 and
1981; the observed incidence rates showed an excess of
cases in Caucasian population and a fewer than expected
among Mexicans, Blacks and Oriental populations [20].
There have also been other studies, as indicated below, in-
cluding the SEARCH, Philadelphia Registry, Allegheny and
the Colorado IDDM studies. The SEARCH study was de-
signed to identify incident and prevalent cases among sub-
jects less than 20 years of age to estimate the incidence and
prevalence of T1D by age, gender and ethnic groups. These
reports showed an increment in the incidence of the disease
(14.8/100,000/year (CI 14.0-15.6) in 1978-1988 vs
23.9/100,000/year (CI 22.2-256) in 2002- 2004 with no sta-
tistical differences in the percentage increase in incidence
rate between ethnic groups. Nevertheless, the lowest rates
were observed in Hispanics (10.7/100,000 for girls and
7.5/100,000 for boys) from 1978-1988 and 2002-2004. The
increase in incidence, however, was significant for both His-
panic (1.6 % (CI 0.2-3.1) per year) and non-Hispanic-white
(2.7% (CI 1.9-3.6) per year) [21]. In contrast, the Philadel-
Type 1 Diabetes in Latin America
phia Registry had consistently reported higher incidences in
Hispanic children compared with other groups living in this
region. Average incidence showed to be 17.8/100,000 per
year between 2000 and 2004, and this issue might be related
to the prevalent Puerto Rican population living in this area
and the higher incidence that has been usually reported for
this Hispanic group compared to others (16.8/100,000 vs
8/100,000 for Brazil and Uruguay, 6/100,000 for Argentina,
3/100,000 for Colombia and Chile and <2/100,000 for Mex-
ico, Paraguay, Peru and Venezuela, according to DIAMOND
Project) [22].
Genetic composition of Puerto Rican people is estimated
to be 50% South European, mostly from Spain, 30% West
Africans, and 20% from other ethnic groups (Amerindian,
North European Caucasians and Asian). The SEARCH rates
for Hispanics were similar to those reported for Puerto Rican
children in Philadelphia, but higher than those reported in
Colorado. However, direct comparisons are not possible be-
cause major methodological differences exist between stud-
ies as well as the percentage of cases having type 2 diabetes,
and because some studies compare white and non-white,
while others compare Hispanic and non-Hispanic, popula-
tions.
GENETIC RISK FACTORS
T1D is a multifactorial and polygenic disease that exerts
a high genetic susceptibility trait with a concordance rate in
twins of about 30-50%. Genetic variants of the Human Leu-
kocyte Antigen (HLA) on chromosome 6p21.3, particularly
combinations of DR3/DR4 produce the highest risk. It ex-
plains nearly 50% of the genetic contribution. Other non-
HLA T1D susceptibility genes include the insulin gene (INS)
on chromosome 11p15, the polymorphic, cytotoxic T-
lymphocyte associated protein a (CTLA4) gene on chromo-
some 2q33, the protein tyrosine phosphatase, non-receptor
type 22 (PTPN22) gene on chromosome 1p13, the interleu-
kine 2 receptor, alpha (IL2RA) and interferon induced with
helicase C domain (IFIH1) genes [23].
Regrettably, the Latin American populations and the
Amerindian individuals have been underrepresented in the
T1D genetic studies. For example, several T1D genome wide
association studies (GWAS) have been published [24]. The
T1DGC GWA study, meta-analysis and replication study
included data from more than 30,000 individuals mainly of
Caucasian origin. A recent meta-analyses on this issue recol-
lected GWAS data from 9,934 cases/16,956 controls. The
results were replicated in 1120 case-parent trios. However, a
large percentage of individuals were of Caucasian ancestry
[25]. The inclusion of individuals with other ethnic back-
grounds is highly desirable. It may narrow the large loci in
which association have been detected. Furthermore, this ap-
proach increases the likelihood to detect rare variants with
major effects. Inclusion of Amerindians have resulted in
novel findings in the study of common diseases [26,27].
Thus, future GWAS study may consider the inclusion of
ethnic diverse populations composed by both high (i.e. Cau-
casian) and low (i.e. Amerindians) incidence groups
Collado-Mesa and coworkers analyzed the possible cor-
relations between T1D incidence and prevalence with some
risk factors (including ethnicity, geographical latitude,
Current Diabetes Reviews, 2014, Vol. 10, No. 2 5
breast-feeding history, per capita coffee consumption and
milk supply in Latin American). A detailed search of data
concerning composition of populations, particularly the per-
centage of Amerindian people in each country was obtained.
Most of the information regarding the rest of the variables
was taken from the United Nation and United Nations Chil-
dren´s Fund program. A strong negative correlation was
found between T1D incidence and the proportion of Amer-
indians in the total population (r=-0.75; p=0.008). Further-
more, a positive correlation was found with the per capita
milk supply per year (r=0.70; p=0.025) and no significant
correlations were found with any other indicators [28]. These
results could be partially explained by a low genetic suscep-
tibility of Amerindian population as well as to a continuous
exposure to protective environmental factors or reduced ex-
posure to risk factors. Two decades ago some genetic studies
had already suggested that low frequency of DR3 haplotypes
in the general population of Colombia, Venezuela and Mex-
ico accounted for low incidences of T1D [28, 29]. A US
study evidenced that protective DRB1*1402 haplotype was
absent in Caucasian population and common in Hispanics
with Native American origin and low rate incidence of T1D
(mainly Mexican-Americans) [30]. The WHO DIAMOND
Molecular Epidemiology sub-project tested the hypothesis
that variation on expression of some T1D susceptibility
genes could influence the incidence of the disease among
participating countries (mainly DQA1 and DQB1 alleles
with sequences coding for arginine in position 52 of the
DQ
-chain, and amino acid other than aspartic acid in posi-
tion 57 of the DQ-chain, respectively) [31]. Data from 12
populations that had completed recruitment at that time were
considered for analysis. Low and very low incidence coun-
tries included Chile, Mexico, Peru, Japan, China and Korea;
high incidence was represented by Finland, Spain and Ar-
gentina. DQA1*0301 was the only DQA1 allele to be consis-
tently associated with T1D across populations. DQA1*0301
occurred with a higher frequency in the low incidence Asian
and Latin American countries, therefore it seems to be a reli-
able marker of the disease in these populations. DQB1*0201
and DQB1*0302 were significant markers of T1D suscepti-
bility in all populations except Japan. These alleles were
more prevalent in the moderate-high and low incidence Latin
American compared to low incidence Asian countries.
In all countries the higher risk was associated to DQB1
non-Asp 57/DQA1 Arg 52 homozygotes containing alleles,
while DQB1*602 was universally protective. These data
reveal considerable variation in the frequencies of DQB1 and
DQA1 alleles across countries, which may partially explain
variations in incidence patterns.
Cruz-Tapias and coworkers published a meta-analysis
designed to estimate the risk associated with variations in
HLA Class II in some autoimmune diseases, including T1D,
in Latin American countries. Major risk alleles related to
T1D incidence showed to be DQA1*301/*501,
DQB1*201/*302/*301 and DQB1*401/*402/*405, while the
protective ones were DQB1*501, DQB1*602/*603, as well
as DQB1*11/*13/*14/*15 [32]. Gorodezky and coworkers,
identified the following haplotypes as those with the strong-
est association with T1D in Mexicans: DRB1*0301-
DQA1*0501-DQB1*0201 (OR=21.4); DRB1*0405-
DQA1*0301-DQB1*0302 (OR=44.5) and the same
6 Current Diabetes Reviews, 2014, Vol. 10, No. 2
DQA1/DQB1 with DRB1*0404/*0401 conferring lower
risk, increasing (OR=61.3) with an early age at onset and a
heterozygote DR3/DR4 genotype [33]. A study conducted in
Santiago de Chile has described that alleles
DQB1/*201(OR=4.7 CI 1.9-11.6) and DQB1/*302 (OR=7.2
CI 2.8-18.5) are strongly associated with the disease in this
population. When case-parent trios were used, alleles
DQB1*302 and DQB1*201 were similarly associated with a
higher risk of T1D [34]. Similar findings have been proposed
for Uruguayan population, DQB1*302/DQB1*201 (33%,
RR=5.41, p<0.05) being significantly associated with the
disease [13].
In summary, it is tempting to postulate that the lower in-
cidence of T1D reported in populations with a high Amerin-
dian background could result from a low prevalence of the
susceptibility alleles common in other ethnic groups and the
potential existence of protective alleles that are derived from
the Amerindian heritage [33]. Thus, ethnicity is a major con-
founding variable to be controlled by the study design and
the proper selection of ancestry markers.
NON-GENETIC RISK FACTORS
The growing incidence of T1D reported in the majority
of the regions during the past few years cannot be explained
by shifts in the distribution of the risk alleles. Brisk changes
in the incidence of any condition could be explained only by
modifications on environmental factors. However, cause-
effect relationships between T1D and environmental risk
factors are difficult to be established. Environmental factors
are thought to be triggers of beta-cell autoimmunity. The
agents may act directly on the pancreas or provoke abnormal
immune responses to proteins normally expressed in the
cells.
Twin studies suggest an important role of environmental
conditions in the development of T1D. The concordance of
type 1 diabetes development differs much more dramatically
between monozygotic and dizygotic twins. Monozygotic
twins living on different environments have a dissimilar risk
for developing T1D; the lack of agreement of the risk is pro-
portional to the length of the residence in diverging settings
[35].
Environmental factors such as diet and viral infection
have been associated with an increased risk of T1D in ge-
netically susceptible individuals. The epidemiological data
suggest that some viruses have been claimed to unchain T1D
inducing autoimmunity or facilitating this process by mo-
lecular mimicry or non-specific activation mediated by cyto-
kines. The possible mechanisms may be involved in the virus
infection-mediated development of T1D is via a direct cyto-
lytic effect, and through triggering autoimmune responses
gradually leading to
-cell destruction. It has also been sug-
gested that epigenetic and environmental changes are in-
volved in imprinting control regions, and mutations of the
binding motif of ZFP57 has been linked to type 1 diabetes
[36, 37]. Coxsackie virus infections, which contain a peptide
homologous to glutamic acid decarboxylase 65 (GAD65),
are often observed in childhood and are known to have ef-
fects on the pancreas. However, the response is probably not
T1D specific, since antibodies have been found in healthy
controls as well. Early exposure to enterovirus such as cox-
Gómez-Díaz et al.
sackie virus B, mumps, rubella, cytomegalovirus, parvovi-
rus, rotaviruses, and encephalomyocarditis virus might con-
tribute to T1D pathogenesis. Ten percent of children with
congenital rubella infection and the HLA susceptibility
markers develop T1D [38,39]. Recently, Mycobacterium
avium subsp. paratuberculosis (MAP) has been proposed as
a new environmental trigger that might contribute to T1D
pathogenesis [40,41]; these organisms, are found in water,
soil, and aerosols. Despite some of these pathogens are
common in Latin American countries, the available informa-
tion is scant. Much remains to be learned about transmission
of infection and pathogenesis of the T1D in Latin-American
population.
Contradictory opinions exist regarding several dietary
factors and T1D. In Finland, almost all infants with recent
diagnosis had a cellular or humoral response against bovine
serum albumin or milk casein [42]. Additionally, intake of
vitamin D either from food or supplements during pregnancy
has been postulated as a trigger, but negative results have
been reported in Finnish offspring carrying increased genetic
susceptibility to T1D [43]. Latin American countries are
having major changes in their dietary habits during the past
five decades. The socioeconomic shifts of the region are
natural experiments to explore the role of pathogens and diet
components in the pathogenesis of T1D. Since environ-
mental agents will not always are easy to be measured, many
epidemiologic investigations will require patient samples on
a large-scale. Multicenter international efforts are needed to
collect the large number of samples. It will take time to
benefit fully from a systematic exploration of all available
population and hospital databases providing historical and/or
prospective information on the history of infections, drug
use, and natural or industrial environmental exposures, such
as has been proposed by Pierre Bougnères and Alain-Jacques
Valleron [44].
On other hand, a contributing factor for the growth of
diabetes cases in the young is the increment of the mean
body mass index of the population. Non-Caucasian popula-
tions have a higher susceptibility for type 2 diabetes; the risk
surges even with a modest accumulation of visceral fat. The
number of cases with type 2 diabetes has scaled up in Latin
American countries during the past few decades. The contri-
bution of type 2 diabetes among the young population with
diabetes is significantly greater in non Caucasians. Even
more, the clinical distinction between the main forms of dia-
betes is difficult in some cases leading to a potential overes-
timation of the T1D incidence. Thus, pre-specified con-
founding variables (i.e. body mass index and family history
of type 2 diabetes) should be recorded and controlled in fu-
ture diabetes registries including non-Caucasian individuals.
QUALITY OF CARE AND SPECIAL PROGRAMS IN
LATIN AMERICA
Life expectancy has grown remarkably during the past
few decades for T1D patients due to changes in access and
provision of health services. Data from the Pittsburgh Epi-
demiology of Diabetes Complications (EDC) Study cohort
compared the life expectancy of T1D cases stratified by the
year of diagnosis (1950-1964 (n = 390) vs. 1965-1980 (n =
543)). Death occurred in 237 (60.8%) of the 1950-1964 sub-
Type 1 Diabetes in Latin America
cohort compared with 88 (16.2%) of the 1965-1980 subco-
hort. The life expectancy at birth for those diagnosed 1965-
1980 was 15 years greater than participants diagnosed 1950-
1964 (68.8 [95% CI 64.7-72.8] vs. 53.4 [50.8-56.0] years,
respectively (p= 0.0001); the difference remained statisti-
cally significant even after adjusting for confounding vari-
ables. Authors identified that early deaths and a decreased
incidence of acute complications as the most likely explana-
tion for the prolonged life span [45]. Despite the general
belief that the same trend is occurring in other areas, no pub-
lished evidence exists to support this assumption in Latin
America. Such information is crucial to adjust treatment
programs.
Quality of care is difficult to measure. Nevertheless, it
consists of three main principles: 1) knowledge, attitude and
clinical practice of health care professionals; 2) patient ac-
cess to care, insulin, medications and the elements for the
control and treatment of the illness; and 3) motivation and
active participation and adherence of the patient in the treat-
ment [46]. Very little has been written about the quality of
health care in Latin America for patients with type 1 diabe-
tes. Nevertheless, it is known that health care varies between
countries and regions within countries, often due to logistic
barriers, ethnic considerations or sociodemographic condi-
tions. Since clinicians often focus on the complications, such
as cardiovascular or renal, treatment of diabetes is undere-
valuated. Distance to and distribution of hospitals and clinics
affect the accessibility to care of rural and suburban areas.
Countries with higher illiteracy and poverty and lower life
expectancy tend to have poorer quality of care, and have a
great disparity in health services [47].
In August, 1996, the Pan-American Health Organization
approved the Declaration of the Americas on Diabetes
(DOTA) [48], which calls for the establishment of programs
to eliminate the inequalities in care, to promote improved
treatment and to create national programs in the member
countries with specific strategies for these and related goals,
which include:
• Recognizing diabetes as a growing and costly health
issue.
• Formulating well-defined and specific programs
against diabetes in each country.
• Offering quality, sanitary health care and promoting
healthy lifestyle changes.
• Assigning the necessary resources to achieve these
goals.
• Designing care models that include both health care
professionals and patients, combining care and educa-
tion.
• Assuring of the availability of care and treatment.
• Assuring adequate education and knowledge of both
patients and health care professionals.
• Implementing public information systems about type
1 diabetes [48].
In response, several Latin American countries have im-
plemented carefully-designed programs to deal with type 1
diabetes (see Fig. 1), such as the Diabetes Initiative for the
Current Diabetes Reviews, 2014, Vol. 10, No. 2 7
Americas (DIA), Quality Control of Care for People with
Diabetes Mellitus (QUALIDIAB), Program for the Preven-
tion, Care and Treatment of People with Diabetes
(PROPAT), and the Foundation for the Prevention and Con-
trol of Non-Transmissible Chronic Diseases in Latin Amer-
ica (FunPRECAL). Universal access to insulin therapy was
considered as an obligation for all governments.
DIA relies on three lines of action: 1) improve the avail-
ability and use of epidemiological information; 2) promote
the reasonable use of available resources; and 3) promote the
design and implementation of educational and self-mana-
gement programs adapted to socio-cultural characteristics of
the region [49]. It has been implemented in countries such as
Bolivia.
QUALIDIAB is another program that has shown success
in tests in Latin America. It is considered the ideal instru-
ment for checking the quality of care for people with diabe-
tes in Latin America and the Caribbean, identifies defects in
the quality of care for diabetic patients to implement appro-
priate interventions to improve it. This allows improving the
quality of life of patients, optimize the use of resources and
reduce the socioeconomic costs of this disease. [46].
PROPAT was implemented in 1998 in Argentina, and was
proven to be successful in studies published in 2000 [50] and
2013 [51]. FunPRECAL is a program that, by 2010, existed
in 10 Latin American countries: Argentina, Brazil, Colom-
bia, Cuba, Ecuador, Guatemala, Mexico, Paraguay, Peru and
Uruguay. Studies have also shown that it is a successful pro-
gram in reducing both co-morbidities and costs [52].
Several international entities had implemented specific
programs to support diabetes treatment programs and use of
insulin in developing areas of the region [53]. In addition,
multiple initiatives to improve treatment of chronic diseases
management are under way in the region. The programs are
reviewed in detailed elsewhere [54].
COMPLICATIONS AND COSTS IN LATIN AMERICA
It is well accepted that patients with type 1 diabetes suf-
fer a broad range of complications and co-morbidities. The
above-mentioned programs have proven successful in reduc-
ing the frequency and severity of these conditions. Compli-
cations to be avoided include: hypertension, obesity, micro-
albuminuria, retinopathy, ketoacidosis, chronic kidney dis-
ease [49], micro and macrovascular complications [55]. It
has been suggested that the presence of diabetes increases
the probability of abdominal obesity in type 2 diabetes [56].
These complications can account for up to 50% of the over-
all costs of type 1 diabetes. In addition, these conditions not
only affect the patient’s quality of life, but cause increased
hospitalizations, loss of production and early retirement.
It is very difficult to compare the costs of type 1 diabetes
within Latin America, due to the variety of health care pro-
grams and economic conditions. In fact, few reports exist
with this information. Most reports examine type 2 diabetes,
but avoid consideration of type 1. When looking at the re-
ports that do exist, it is important to take into account the
factors included, such as the number of medical visits, hospi-
talizations, and whether insulin use, tests and other inciden-
tals are considered. In many countries, availability of serv-
8 Current Diabetes Reviews, 2014, Vol. 10, No. 2
Fig. (1). Multiple Latin American initiatives designed to control type 1 diabetes.
ices and socioeconomic factors of the population come into
play. Nevertheless, in a study in the U.S., it was determined
that type 1 diabetes is more costly than type 2. In that study,
it was determined that the average annual cost per patient of
those under 44 years of age was $8,649, while the cost for
patients over 65 increased to $35,365. The annual cost to the
nation was $10.5 billion in direct costs, plus another $4.4
billion in indirect costs, without taking into account co-
morbidities and their consequences, such as the cost of dialy-
sis [57].
In a similar study in Argentina, it was determined that di-
rect costs per patient per month ranged from $756.65 USD to
$1,387 USD. This study considered 11 hospitalizations and
an average of 9.3 visits to the doctor per year [49]. Another
study, also in Argentina, considering an average of 10 annual
visits to the doctor, reported direct costs of $55,421 USD per
year per patient, without considering the costs directly re-
lated to co-morbidities [52].
Gómez-Díaz et al.
In Brazil, the situation is very different. There, the direct
cost per patient per year was reported as being $ 1,319.15
USD, with treatment –related costs accounting for 92.2% of
this total ($ 1,216.33 USD). That study considered only 3
visits to the general practitioner per year, plus 1 visit to the
ophthalmologist, 1 test of HbA1c, 1 lipid profile, 1 EKG and
1 urine test. Interestingly, this study found that costs in-
creased by half in cases of patients with less than 5 years of
diagnosis compared with those with over 15 years of diagno-
sis. Nevertheless, in the period 2008-2010, the overall cost to
the country was estimated at $ 4,194,892 USD [55].
It should be noted that most of the studies agree that the
implementation of programs increases the direct cost of care
for type 1 diabetes. This is due to increased awareness by
both public and healthcare professionals, improved diagnosis
techniques and frequency, and increased intervention pro-
grams. On the other hand, these gains are reflected in de-
creased co-morbidities, although they incur higher costs.
Type 1 Diabetes in Latin America
AREAS OF OPPORTUNITY
Chronic diseases are the main health challenge for the
Latin America region. Although T1D contributes with a rela-
tively small number of users of the health systems, it is nec-
essary to have a structured action plan to control the burden
of the disease due to the cost and complexity of the treat-
ment. The provision of health services should be adapted the
specific needs of patients with chronic diseases and the exist-
ing resources of the health system.
T1D is an area in which innovative low cost management
plans could be designed and applied. The characteristics of
some of the Latin American health systems facilitate the
implementation of translational research programs in this
field. The high cost derived of the frequent and complex use
of emergency services could be ameliorated by changes in
self-management support using electronic media, toolkits
and the participation of multidisciplinary teams. Patients and
their families should be empowered to take care of the day-
to-day adjustments of their treatment using standardized pro-
cedures. Internet or cell phone approaches have proved to be
valuable support tools to improve the decision making proc-
ess, adherence and prevention of acute complications. Sev-
eral decision support tools have been developed for patients
and physicians. Its integration to the electronic records is
feasible and desirable. In order to have organized clinical
practices in accordance with local guidelines, it is crucial to
have electronic (or even in paper) sheets with pre-specified
assessment schemes and outcomes. This is the first step to
create registries and surveillance networks.
Limited budgets and the lack of the required personnel is
a major barrier, especially in developing countries. The cost
of medications and medical devices could be lowered with
the organizational changes in the health system, pooled pro-
curement programs and the use of generics. At distance
training programs for health professionals should move from
being a source of information to become an accessible option
to develop specific clinical competences (i.e. prevention of
hypoglycemia or treatment adjustments during sick days).
Involvement of patients or their relatives in community pro-
grams (as certified heath coaches or as group coordinators) is
an option to make available services. Involvement of medi-
cal societies and creation of partnerships with stakeholders
are crucial to have an effective advocacy and complimentary
funds.
On the other hand, the rapid socioeconomic changes oc-
curred in the past few decades in the region and the admixed
nature of the population are unique opportunities to measure
the contribution of environmental and genetic factors.
Multidisciplinary efforts and interaction between Latin
American research groups are needed to generate these ini-
tiatives.
CONCLUSIONS
In summary, the study of T1D in Latin America offers
new venues to generate knowledge about the role of genetics
and environment in the pathogenesis of T1D and for the de-
sign and validation of innovative approaches to manage the
disease. Remarkable changes in socioeconomic conditions
have occurred in Latin America in the past five decades. As
Current Diabetes Reviews, 2014, Vol. 10, No. 2 9
a result, the prevalence of infectious diseases and obesity has
undergone brisk modifications. These evolving environ-
mental phenomena are opportunities to assess the role of
known risk factors for T1D and to detect new associations.
Furthermore, the Amerindian heritage of the population
could be a source of information to detect new T1D genetic
variants. Finally, the limited budgets of the Latin American
countries should be a stimulus for creating innovative assis-
tance programs, in which patients are empowered by
multidisciplinary teams that applies at-distance communica-
tion tools to support the patient’s decision making process.
International coalitions are critical to make use of the poten-
tial opportunities that offers Latin America for the study of
T1D.
CONFLICT OF INTEREST
The authors confirm that this article content has no
conflict of interest.
ACKNOWLEDGEMENTS
There are no conflicts of interest. The authors thank Ms.
Susan Drier Jonas for her assistance with this manuscript.
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Accepted: February 20, 2014