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Erschienen in: BMC Public Health 1/2015

Open Access 01.12.2015 | Research article

Global epidemiology of type 1 diabetes in young adults and adults: a systematic review

verfasst von: Paula A Diaz-Valencia, Pierre Bougnères, Alain-Jacques Valleron

Erschienen in: BMC Public Health | Ausgabe 1/2015

Abstract

Background

Although type 1 diabetes (T1D) can affect patients of all ages, most epidemiological studies of T1D focus on disease forms with clinical diagnosis during childhood and adolescence. Clinically, adult T1D is difficult to discriminate from certain forms of Type 2 Diabetes (T2D) and from Latent Autoimmune Diabetes in Adults (LADA).
We searched the information available worldwide on the incidence of T1D among individuals over 15 years of age, and which diagnostic criteria should be used use to qualify T1D in adults. We then studied the variation of T1D incidence with age in adults, and compared it to the incidence in the <15 years-old.

Methods

A systematic review of the literature was performed to retrieve original papers in English, French and Spanish published up to November 6, 2014, reporting the incidence of T1D among individuals aged over 15 years. The study was carried out according to the PRISMA recommendations.

Results

We retrieved information reporting incidence of T1D among individuals aged more than 15 years in 35 countries, and published in 70 articles between 1982 and 2014. Specific anti-beta-cell proteins or C-peptide detection were performed in 14 of 70 articles (20%). The most frequent diagnostic criteria used were clinical symptoms and immediate insulin therapy. Country-to-country variations of incidence in those aged >15 years paralleled those of children in all age groups. T1D incidence was larger in males than in females in 44 of the 54 (81%) studies reporting incidence by sex in people >15 years of age. The overall mean male-to-female ratio in the review was 1.47 (95% CI = 1.33-1.60, SD = 0.49, n = 54, p = <0.0001). Overall, T1D incidence decreased in adulthood, after the age of 14 years.

Conclusions

Few studies on epidemiology of T1D in adults are available worldwide, as compared to those reporting on children with T1D. The geographical variations of T1D incidence in adults parallel those reported in children. As opposed to what is known in children, the incidence is generally larger in males than in females. There is an unmet need to evaluate the incidence of autoimmune T1D in adults, using specific autoantibody detection, and to better analyze epidemiological specificities – if any – of adult T1D.

PROSPERO registration number

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Electronic supplementary material

The online version of this article (doi:10.​1186/​s12889-015-1591-y) contains supplementary material, which is available to authorized users.

Competing interests

The authors declare that they have no competing interests.

Authors’ contributions

PAD-V conducted the data collection and analyses. PAD-V, PB and AJV, contributed to the writing of the manuscript. All authors read and approved the final manuscript.

Background

The worldwide epidemiology of childhood Type 1 diabetes (T1D) was extensively described in the 6th edition of the International Diabetes Federation (IDF) [1]. Data were retrieved in approximately 45% of the countries [1-4]. In contrast, we are unaware of a similar review on the worldwide epidemiology of adult T1D diabetes, although T1D is known to occur even late in adults [5-7]. A major limitation of the epidemiology of T1D in adults is certainly the difficulty there is to distinguish it from Type 2 diabetes (T2D) requiring insulin treatment or from Latent Autoimmune Diabetes in Adults (LADA), when specific markers of autoimmunity are not searched.
Here, our primary objective was to describe – through a systematic review of the literature – the available published information on adult T1D incidence, and the diagnostic criteria used for case definition. A secondary objective was to study how the variations of T1D incidence in adults mirrored those in children.

Methods

Literature review

A systematic review was conducted according to the PRISMA recommendations to retrieve original papers published in English, French and Spanish up to November 6th, 2014, in peer-reviewed journals reporting the incidence of T1D among individuals aged more than 15 years, in population-based studies (i.e. collected in a defined geographic area [8]) and reporting the diagnostic criteria used to define T1D.
The databases used for the literature search were Medline (PubMed), Google Scholar and Thomson Reuters (Web of Knowledge). The protocol of the search was registered in the International Prospective Register of Systematic Reviews (PROSPERO) and is available on http://​www.​crd.​york.​ac.​uk/​PROSPERO/​display_​record.​asp?​ID=​CRD42012002369 (Registration number: 2012:CRD42012002369). Figure 1 presents the flow diagram of the bibliographic search, Additional file 1 for the full electronic search strategy, and Additional file 2 for the PRISMA checklist.

Data collection

For each study, the following information was extracted:
  • the identification of the study: authors, title, journal, publication year,
  • the period and country of study. The country was categorized by its World Health Organization (WHO) region and economic level: high-income (HIGH) or low- and middle-income (LMIC) [9],
  • the geographic coverage of the study: nationwide (when the study was performed in the entire nation) and local (when it was restricted to a given region, city, or a geographically defined population),
  • the diagnostic criteria used to define T1D in adults: detection of autoantibodies against beta-cells (such as: islet cell antibody (ICA), insulin autoantibody (IAA), islet antigen-2 autoantibody (IA-2), anti-glutamic acid decarboxylase antibodies (GAD)), measurement of the fasting C-peptide level [7], need for permanent insulin therapy, time when the administration of insulin therapy was started, and clinical signals of T1D diabetes such as ketosis, ketonuria and weight loss,
  • the sources of data/registers reporting T1D incidence in the studies, defined according to LaPorte et al. [10] as: primary source of information: a “well-established system of standardized registries for identifying new cases”, for example national or regional registers, secondary source of information: other different sources of cases “that would provide a check on the degree of ascertainment”, for example medical records or hospital discharges, and tertiary source of information: a third approach for identifying cases, for example, through surveillance system or death certificates,
  • the reported percentage of completeness/ascertainment between sources of information reporting incidence [10],
  • the incidence rates reported in the text, tables or graph (expressed as new cases per 100.000 persons/year) by sex and age classes,
  • additional information such as those concerning rural/urban, or ethnic differences.

Data analyses

The country distribution of the T1D incidence information and the analysis of the diagnostic criteria used were performed on the entire set of articles retrieved. For the few papers for which the results were presented by ethnic origin, we estimated the mean value of the incidence for the given period in the countries/regions concerned.

Correlation between adult and children T1D incidences

In the geographical correlation analyses between children and adult incidences, we considered for each country the more recent nationwide study published, or if not available, the last published set of local studies retrieved from a given area in the country; in addition, we included all published papers reporting auto-antibodies against beta-cells or C-peptide. To obtain an estimate of the incidence of T1D in children in the countries for which the adult incidence was available, we used the data provided by the same adult paper, when available. The incidence of T1D in children was not available in 9 of these papers included in the geographical correlation analyses. In this case, it was estimated through a separate systematic review focused on the corresponding countries and periods (see Additional file 3).

Statistics

Data were extracted from graphs using GraphClick [11].
The country-to-country co-variation of children and adult incidences was quantified by the Spearman correlation and a linear regression.
The R software (version 3.0.1) was used for statistical and graphic analyses [12].

Results

Description of the information obtained from the systematic review on adult T1D

Seventy articles reporting incidence of T1D in young adults and adults aged over than 15 years concerned one country, and one article concerning two countries were retrieved in this systematic review, resulting in a total of 71 studies covering 35 countries (Table 1). Twenty-four of the 71 studies were nationwide; 43 papers provided information on the T1D incidence in the age class 15–29 years, 26 in the age class 30–59 years, and 6 in the persons aged >60 years.
Table 1
Systematic review of T1D in adults, diagnostic criteria and sources of information
Study information
T1D diagnosis criteria in adults and young adults
Source of information and validation of ascertainment between sources
Country, area reported in the article
First author, publication year
Ref
Age range
Period
Detect. AA/C-Peptide
Need of insulin therapy
Administration insulin therapy
Clinical impression
Ketosis/ ketonuria
Weight loss
Primary
Secondary
Tertiary
% of ascertainment
African Region, LMIC
Mauritius: NW
Tuomileht J., 1993
[13]
0-19
1986-1990
No
Yes
From diagnosis
Yes
NA
NA
Medical reports
Medical statistics
NA
95.0
United Republic of Tanzania: Dar es Salaam
Swai A. B., 1993
[14]
0-19
1982-1991
No
Yes
From diagnosis
Yes
NA
NA
Medical reports
Hospital records
NA
NA
Eastern Mediterranean Region, LMIC
Iran (Islamic Republic of): Fars
Pishdad G. R., 2005
[15]
0-29
1990-1994
Yes (a)
Yes
From diagnosis
Yes
Yes
Yes
Medical reports from endocrinologists
Medical records
NA
100
Libyan Arab Jamahiriya: Benghazi
Kadiki O. A., 1996
[16]
0-34
1981-1990
No
Yes
From diagnosis
NA
Yes
NA
National Diabetes Program
Hospital registers
NA
95.0
Tunisia: Beja, Monastir, Gafsa
Ben Khalifa F., 1998
[17]
0-19
1990-1994
No
Yes
From diagnosis
Yes
NA
NA
Hospital records
School health centers
NA
96.0
European Region, LMIC
Croatia: Zagreb
Roglic G., 1995
[18]
0- > 55
1988-1992
No
Yes
Within 1 week of diagnosis
Yes
Yes
NA
National Diabetes Program
Death certificates
Diabetes association
96.2
Estonia: NW
Kalits I., 1990
[19]
0- > 50
1988-1988
No
Yes
From diagnosis
Yes
Yes
Yes
NA
NA
NA
NA
Lithuania: NW
Ostrauskas R., 2011
[20]
15-34
1991-2008
No
Yes
Within 2 weeks of diagnosis
Yes
Yes
Yes
National Diabetes Program
Regional endocrinologist
Notes of patient insurance
86.8
Lithuania: NW
Pundziute-Lycka A., 2003
[21]
0-39
1991-2000
No
Yes
Within 2 weeks of diagnosis
Yes
Yes
NA
National Diabetes Program
Pediatrician and endocrinologist reports
Death certificates
91.2
Lithuania: NW
Ostrauskas R., 2000
[22]
15-39
1991-1997
No
Yes
Within 2 weeks of diagnosis
Yes
Yes
NA
National Diabetes Program
Pediatrician and endocrinologist reports
Death certificates
91.2
Poland: Bialystok
Kretowski A., 2001
[23]
0-29
1994-1998
No
Yes
From diagnosis
Yes
Yes
Yes
Pediatric and Internal medicine records
Hospital discharge registers
NA
98.5
Poland: Province of Rzeszow
Sobel-Maruniak A., 2006
[24]
0-29
1980-1999
No
Yes
From diagnosis
Yes
NA
NA
Pediatric and Internal medicine records
Others health care registers
NA
99.0
Poland: Province of Rzeszow
Grzywa M. A., 1995
[25]
0-29
1980-1992
No
Yes
From diagnosis
Yes
NA
NA
Pediatric and Internal medicine records
Others health care registers
NA
99.0
Poland: Warsaw
Wysock M. J., 1992
[26]
0-29
1983-1988
No
Yes
From diagnosis
Yes
NA
NA
Medical records from diabetic clinics
General practitioners and diabetologist registers
Death certificates
NA
Romania: Bucharest
Ionescu-Tirgoviste C., 1994
[27]
0- ≥ 85
1981-1991
No
Yes
From diagnosis
Yes
Yes
NA
Bucharest Diabetes Registry
NA
NA
NA
Slovakia: NW
Kyvik K O, 2004
[28]
15-29
1996-1997
No
Yes
From diagnosis
Yes
NA
NA
Pediatrician and endocrinologist reports
Other health care registers
NA
80.0
European Region, HIGH
Austria: Upper
Rami B., 2001
[29]
0-29
1994-1996
No
Yes
From diagnosis
Yes
NA
NA
Pediatricians and endocrinologists reports
Austrian Diabetes Association
NA
87.0
Belgium: Antwerp
Weets I., 2007
[30]
0-39
1989-2003
Yes
Yes
From diagnosis
Yes
NA
NA
Pediatricians and endocrinologists reports
General practitioners and diabetes nurses reports
Diabetes associations and self-reporting
97.0
Belgium: Antwerp
Weets I., 2002
[31]
0-39
1989-2000
Yes
Yes
From diagnosis
NA
NA
NA
Pediatrician and endocrinologist reports
General practitioner and diabetes nurse reports
Diabetes associations and self-reporting
93
Belgium: Antwerp
Vandewalle C., 1997
[32]
0-39
1989-1995
Yes
Yes
From diagnosis
Yes
Yes
Yes
Pediatrician and endocrinologist reports
General practitioner and diabetes nurse reports
Diabetes associations and self-reporting
85
Bosnia and Herzegovina: Republic of Srpska
Radosevic B., 2013
[33]
0-18
1998-2010
No
Yes
From diagnosis
Yes
NA
NA
Hospital records
Insulin prescription registers
NA
100
Denmark: Copenhagen and Frederiksborg
Molbak A. G., 1994
[34]
30-95
1973-1977
Yes (b)
Yes
From diagnosis
Yes
Yes
Yes
Hospital discharges
General practitioners and diabetologist registers and death certificates
Missing coding of T1D diagnosis in hospital admissions
99.0
Finland: NW
Lammi N., 2007
[35]
15-39
1992-1996
Yes
Yes
From diagnosis
Yes
NA
NA
National Diabetes Program
Hospital discharge registers
Drug reimbursement registers
88.0
France: Aquitaine, Lorraine, Basse Normandie, Haute Normandie
Charkaluk M. L, 2002
[36]
0-19
1988-1997
No
Yes
None declared
NA
NA
NA
Prospective registers
French Social Security registers
NA
96.0
France: Aquitaine, Lorraine, Basse Normandie, Haute Normandie
Levy-Marchal, C., 1998
[37]
0-19
1988-1995
No
Yes
None declared
NA
NA
NA
Prospective registers
French Social Security registers
NA
96.0
Israel: NW
Blumenfeld O., 2014
[38]
0-17
1997-2010
No
Yes
From diagnosis
Yes
NA
NA
Israel juvenile diabetes register
Israel Center for Disease Control
NA
NA
Israel: NW
Sella T., 2011
[39]
0-17
2000-2008
No
Yes
None declared
Yes
NA
NA
Israel juvenile diabetes register
Israel Center for Disease Control
NA
NA
Israel: NW
Koton S., 2007
[40]
0-17
1997-2003
No
Yes
From diagnosis
Yes
NA
NA
Israel juvenile diabetes register
NA
NA
NA
Italy: Lombardie
Garancini, P., 1991†
[41]
0-34
1981-1982
No
Yes
None declared
NA
NA
NA
Hospital discharge records
Hospital admission records
NA
85.7
Italy: Pavia
Tenconi M. T., 1995
[42]
0-29
1988-1992
No
Yes
From diagnosis
Yes
NA
NA
Hospital records
Drug registers
NA
100
Italy: Sardinia
Muntoni S, 1992
[43]
0-29
1989-1990
No
Yes
From diagnosis
Yes
NA
NA
Hospital records
Diabetes association
NA
92.8
Italy: Sardinia (Oristano)
Frongia O., 1997
[44]
0-29
1993-1996
No
Yes
From diagnosis
Yes
NA
NA
Hospital records
Drug registers
NA
100
Italy: Turin
Bruno G., 2009
[45]
15-29
2000-2004
Yes
Yes
Within 6 months of diagnosis
NA
NA
NA
Hospital records
Drug registers
NA
NA
Italy: Turin
Bruno G., 2005
[46]
30-49
1999-2001
Yes
Yes
Within 6 months of diagnosis
NA
Yes
NA
Diabetes clinics
Drug registers
NA
99.0
Italy: Turin
Bruno G., 1993
[47]
0-29
1984-1988
No
Yes
From diagnosis
NA
Yes
NA
Diabetic clinics records
Hospital discharge records
NA
97.0
Luxembourg: NW
De Beaufort C. E., 1988
[48]
0-19
1977-1986
No
Yes
None declared
NA
NA
NA
Pediatric and Internal medicine records
Dutch Diabetes Association
NA
100
Malta: NW
Schranz A. G., 1989
[49]
0-24
1980-1987
No
Yes
Within 3 moths of diagnosis
Yes
Yes
Yes
Medical reports
Diabetic clinic records
NA
NA
Netherlands: NW
Ruwaard D., 1994
[50]
0-19
1988-1990
No
Yes
None declared
NA
NA
NA
Pediatric and Internal medicine records
NA
NA
81.0
Norway: NW
Joner G., 1991
[51]
15-29
1978-1982
No
Yes
From diagnosis
NA
NA
NA
Pediatricians and endocrinologists reports
Hospital records
NA
90.0
Slovenia: NW
Radosevic B., 2013
[33]
0-18
1998-2010
No
Yes
From diagnosis
Yes
NA
NA
Slovenian National Registry of Childhood diabetes
Insulin prescription registers
NA
100
Spain: Badajoz
Morales-Perez F. M., 2000
[52]
0-29
1992-1996
No
Yes
From diagnosis
Yes
Yes
NA
Pediatricians and endocrinologists reports
Diabetic clinic records
NA
95.0
Spain: Canarias Islands
Carrillo Dominguez, A., 2000
[53]
0-30
1995-1996
No
Yes
None declared
Yes
NA
Yes
Hospital records and Endocrinologist reports
Diabetes association reports and sales on blood glucose monitors
NA
90.1
Spain: Catalonia
Abellana R., 2009
[54]
0-29
1989-1998
Yes (c)
Yes
From diagnosis
Yes
Yes
NA
Catalan Registry of Type 1 Diabetes
Summer camps, associations, and prescription data
NA
90.0
Spain: Catalonia
Goday A., 1992
[55]
0-29
1987-1990
No
Yes
From diagnosis
Yes
NA
NA
Catalan Registry of Type 1 Diabetes
Summer camps, patient associations, and prescription data
NA
90.1
Spain: Navarra
Forga L., 2014
[56]
0- > 45
2009-2012
Yes
Yes
Within 6 months of diagnosis
Yes
Yes
NA
Hospital records
Electronic medical records, diabetes associations
NA
98.4
Spain: Navarra
Forga L., 2013
[57]
0-79
2009-2011
Yes
Yes
Within 6 months of diagnosis
Yes
Yes
NA
Hospital records
Electronic medical records, diabetes associations
NA
98.4
Sweden: NW
Dahlquist G. G., 2011
[58]
0-34
1983-2007
No
Yes
From diagnosis
Yes
Yes
Yes
National Diabetes Program
Pediatricians and endocrinologist reports
NA
96.0
Sweden: NW
Östman J., 2008
[59]
15-34
1983-2002
No
Yes
From diagnosis
Yes
NA
NA
National Diabetes Program
Pediatrician and endocrinologist reports
Computer-based patient administrative register
82
Sweden: NW
Pundziute-Lycka A., 2002
[60]
0-34
1983-1998
No
Yes
From diagnosis
Yes
Yes
Yes
National Diabetes Program
Pediatrician and endocrinologist reports
Computer-based patient administrative register
91.2
Sweden: NW
Nyström L., 1992
[61]
0-34
1983-1987
No
Yes
None declared
NA
NA
NA
National Diabetes Program
Hospital admission and discharge registers
NA
89
Sweden: NW
Blohme G., 1992
[62]
15-34
1983-1987
No
Yes
From diagnosis
Yes
Yes
Yes
National Diabetes Program
Hospital admission and discharge registers
NA
NA
Sweden: Kronoberg
Thunander M., 2008
[63]
0-100
1998-2001
Yes
Yes
Within 4 weeks of diagnosis
Yes
Yes
NA
Opportunistic screening of all adult patients in contact with the medical care system
Departments of ophthalmology
NA
98.0
United Kingdom: NW
Imkampe A. K., 2011
[64]
0-34
1991-2008
No
Yes
Within 3 moths of diagnosis
Yes
NA
NA
National Diabetes Program
Pediatricians and endocrinologist reports
NA
NA
United Kingdom: Oxford region
Bingley P. J., 1989
[65]
0-21
1985-1986
No
Yes
From diagnosis
Yes
NA
NA
Medical reports from general practioners and pediatricians
Regional hospital records
NA
95.0
Region of the Americas, LMIC
Barbados: NW
Jordan O. W., 1994
[66]
0-29
1982-1991
No
Yes
From diagnosis
Yes
NA
NA
Hospital records
Others health care registers
NA
94.0
Region of the Americas, HIGH
Canada: Quebec
Legault L., 2006
[67]
0-18
2000
No
Yes
None declared
NA
NA
NA
Departmental program: Régie des Rentes du Québec program
NA
NA
NA
United States of America: Alabama (Jefferson County)
Wagenknecht L. E., 1991
[68]
0-19
1979-1988
No
Yes
None declared
NA
NA
NA
Hospital records
Summer camps, patient associations, and prescription data
NA
NA
United States of America: Alabama (Jefferson County)
Wagenknecht L. E.,1989
[69]
0-19
1979-1985
No
Yes
From diagnosis
Yes
NA
NA
Hospital records
Association registers
NA
95.0
United States of America: Colorado
Vehik K., 2007
[70]
0-17
2000-2004
No
Yes
Within 2 weeks of diagnosis
Yes
NA
NA
Pediatricians and endocrinologists reports
Other health care registers
The SEARCH Study
96.5
United States of America: Colorado
Kostraba J. N., 1992
[71]
0-17
1978-1988
No
Yes
Within 2 weeks of diagnosis
Yes
NA
NA
Pediatricians and endocrinologists reports
Hospital registers
NA
93.3
United States of America: Pennsylvania (Allegheny)
Libman I. M., 1998
[72]
0-19
1990-1994
No
Yes
From diagnosis
Yes
NA
NA
Medical reports
General practitioners and diabetes nurses reports
NA
97.7
United States of America: Rhode Island
Fishbein H. A., 1982
[73]
0-29
1979-1980
No
Yes
None declared
NA
NA
NA
Medical reports
Insulin prescription registers
NA
NA
United States of America: five areas §
Bell R., 2009
[74]
0-19
2002-2005
Yes
Yes
From diagnosis
Yes
NA
NA
Medical reports
Other health care registers
The SEARCH Study
NA
United States of America: Wisconsin
Allen C., 1986
[75]
0-29
1970-1979
No
Yes
From diagnosis
Yes
NA
NA
Hospital discharges
Pediatricians and endocrinologist reports
NA
90.0
United States of America: The United States Navy
Gorham C., 1993
[76]
17-34
1974-1988
No
NA*
None declared
Yes
NA
NA
Hospital discharges
NA
NA
NA
Western Pacific Region, HIGH
Australia: New South Wales
Tran F., 2014
[77]
10-18
2001-2008
No
Yes
NA
Yes
NA
Yes
Endocrine group diabetes register
National diabetes register
NA
96.0
Australia: Sydney (Southern Metropolitan Health Region)
Sutton L., 1989
[78]
0-19
1984-1987
No
Yes
From diagnosis
Yes
NA
NA
Medical reports from general practioners and pediatricians
Schools in the area
Syringe register
NA
Japan: Osaka
Sasaki A., 1992
[79]
0-18
1978-1988
No
Yes
None declared
Yes
Yes
NA
Medical benefits system
NA
NA
NA
New Zealand: Canterbury
Scott, R. S., 1991
[80]
0- ≥ 80
1981-1986
No
Yes
Within 1 year of diagnosis
Yes
NA
Yes
Community-based surveys administrated in pharmacies where diabetic patients acquired their insulin supplies
Hospital admission and discharge registers and diabetologist
NA
95.0
Other Regions currently non WHO
Taiwan: NW
Lin W.-H., 2013
[81]
0- ≥ 60
1999-2010
Yes
Yes
None declared
Yes
Yes
NA
National Health Insure register and Illness certificates
Random sample of a database used to reimbursements
NA
98.3
US Virgin Islands: NW
Washington R. E., 2013
[82]
0-19
2001-2010
No
Yes
From diagnosis
Yes
Yes
Yes
Medical reports
Medical providers
NA
98.7
WHO Member States are divided into high-income (HIGH) or low- and middle-income (LMIC) states [30]. AA: autoantibodies, NW: Nation-wide study, NA: Unavailable data. (a) When there were diagnostic doubts, (b) Only for patients aged over 40 years at onset, (c) Not performed in all cases; the author of this study was contacted to confirm the proportion of these cases, but by the time of submission of this paper no answer was available. T1D: Type 1 Diabetes. Highlighted: reports of the systematic review using the autoantibodies/C-peptide as diagnosis criteria. () Studies used in the statistical analyses. (*) Data were not available but researchers assumed that patients have had T1D based on their average of age. (§) Ohio (8 counties), Washington State (5 counties), South Carolina, Colorado, California.
A primary source of information was reported in 99% (70 of 71) of the studies: among these reported sources, 60% (42 of 70) were from medical/hospital records, 36% (25 of 70) from national or regional registers, and 4% (3 of 70) from other sources, such as community-based surveys; a secondary source of information was reported in 90% (64 of 71) of the studies: among these reported sources, 58% (37 of 64) were from medical/hospital records, 16% (10 of 64) from associations of patients, 14% (9 of 64) from drug or supplies prescription registers, 8% (5 of 64) from national or regional registers, and 5% (3 of 64) from death certificates and schools registers; finally, a tertiary source of information was reported in 21% (15 of 71) of the studies: among these reported sources, 27% (4 of 15) were from national or regional registers, 27% (4 of 15) from associations of patients, 20% (3 of 15) from death certificates, 20% (3 of 15) from drug or supplies prescription registers, and 7% (1 of 15) from medical registers; see details in Table 1. Percentage of ascertainment (completeness) between sources of information was evaluated in 53 of 71 (75%) studies. The mean percentage of ascertainment of these 53 studies was 94% (Table 1).
In the group of young adults (15–19), the lowest incidence of T1D was reported in Mauritius, (1.1/100.000 persons/year) [13], and the highest in Estonia (39.9/100.000 persons/year) [19]. In the 70–79 year age group, the lowest incidence was reported in Navarra, Spain (0.8/100.000 persons/year) [57] and the highest in Kronoberg, Sweden (55/100.000 persons /year) [63]. The details of all retrieved incidence by study and age classes are in Additional file 4: Table S1.

Diagnostic criteria used to define T1D in adults reported in 71 epidemiological studies

Autoantibodies against beta-cell antigens or the C-peptide were included in the T1D diagnostic criteria in 14 studies [15,30-32,34,35,45,46,54,56,57,63,74,81], detection of ICAs was reported in 9 studies [15,30-32,34,45,46,54,63], IAA in 4 studies [30-32,54], IA2 in 5 studies [30-32,56,57], and GAD in 11 studies [30-32,35,45,46,56,57,63,74,81]. The C-peptide was measured in 7 studies. In one paper difference of auto-antibodies by age group (0–19) was explored but no significant differences were detected [74]. The other reported diagnostic criteria for T1D were the need for insulin therapy (reported in 70 of 71 studies), clinical symptoms of diabetes (reported in 56 of 71 studies), low or normal body weight (14 of 71 studies), and ketosis or ketonuria (26 of 71 studies). The details are shown in Table 1.

Comparison of adult and children T1D incidences

The variations of incidence of T1D in adults with country and age were studied in each area for which we retrieved information on a geographically defined population. This concerned 35 countries.

Variation of T1D incidence with age in adults

In 23 out of 35 (66%) countries (55 of 71 studies), the incidence of T1D was higher in the age range of 0–14 compared with 15–19 years. When restricted to the 14 reports for which the criteria of diagnosis of T1D were auto-antibodies against beta-cells or C-peptide detection, the variation of adult incidence with age showed a consistent decrease after the age of 14 years (Figure 2 and Additional file 4: Table S1).

Geographical correlation of adult and child T1D incidence

A significant geographical correlation, as measured by the Spearman correlation coefficient, was found between adult T1D incidence and 0–14 incidence in the age classes 15–19 years, 20–24 years, 25–29 years, 30–34 years and overall in the entire 15–60 group (r = 0.75, p-value: 5.7 × 10−10). The correlation was not significant in the oldest class where sparse data were available, but the relation was similar (Figure 3).

Comparison of male and female T1D adult incidences

T1D incidence was larger in males aged 15 to 39 years than in females in 44 (81%) of the 54 studies reporting incidence by sex (Additional file 5: Table S2). The mean male-to-female ratio in our review was 1.47 (95% CI for mean 1.33-1.60, SD = 0.49, n = 54, p = < 0.0001).

Discussion

A first result of this systematic review is the paucity of data available on adult incidence of T1D as compared to those concerning children. The 71 studies retrieved provided information on adult T1D in only 35 countries, 40% of the 88 countries with primary childhood T1D incidence information in the 6th IDF atlas [1].
A second result is that only a small proportion (n = 14) of the 71 studies used detection of specific autoantibodies and/or dosage of C-peptide [83] as diagnostic criteria of adult T1D.
A third result was that in a majority of the retrieved studies, adult T1D incidence was greater in men than in women, which contrasts with incidence of T1D in children where sex ratio is around one [2,84]. Using comparative data, Karvonen et al. also described a male excess among young adults in the 15–39 years of age [85]. Sex differences in exposure to possible environmental triggers of T1D, in hormonal/genetic susceptibility, in lifestyle have been proposed as possible explanations for this difference [62].
A last striking observation of the current analysis is the strong geographical correlation of the incidences in adults and children. This correlation may be explained by the fact that adults with T1D share the gene alleles known to be associated to incidence of T1D in children, [86,87], and/or some predisposing environmental causes [4]. For example, in a previous study on incidence of T1D in children, a significant positive correlation was detected between the percentage of urban population and the incidence of T1D in children (r = 0.41 p-value: < 0.0001) [4]; in this review a significantly higher urban proportion of T1D incidence among adults was found in 4 of the 7 studies reporting differences between rural vs urban areas [15,21,42,75].
There was an overall decrease of incidence with age in adults and young adults after the age of 14. A second peak of T1D around the age of 50, as described by Krolewski et al. [88], was only reported in 7% (4 of 58) of the studies [18,63,80,89].
The paucity of data made it impossible to document an increase in adult T1D incidence that would parallel the dramatic increase observed in children [2,3,90]. Indeed, successive studies in the same region over different periods reporting incidence in people aged >30 years of age were only found for Belgium [30-32], Lithuania [20-22] and Sweden [58-62]. Similarly, this review did not dispose of sufficient data to document differences in the clinical presentation of T1D of adults and children as suggested elsewhere [32,40]; indeed only two of the 71 studies describe differences in clinical presentation of T1D between adults and children [89,91].
Improving the quantity and quality of information on adult T1D is not only useful to better understand the epidemiology and natural history of T1D, but can have practical consequences, as delay of T1D diagnosis may mean retardation in insulin treatment, lost opportunities for potential prevention of acute and chronic complications, and even death [92]: in Croatia [18], 14% of the incident cases were identified solely through death certificates, and high mortality was found in the newly-diagnosed T1D aged over 50.

Conclusions

Overall, the results of this systematic review should encourage the launching of epidemiological studies of adult T1D with specific diagnostic criteria.

Availability of supporting data

All the supporting data are included as additional files.

Acknowledgements

We thank Anne-Lise Haenni of the Institut Jacques Monod, CNRS - Paris-Diderot University, for critically reading and reviewing the English of this manuscript.

Funding

This study was supported by grants from the Programme Hospitalier de Recherche Clinique, and from Colciencias, the Administrative Department of Science, Technology and Innovation for Colombia. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://​creativecommons.​org/​licenses/​by/​4.​0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://​creativecommons.​org/​publicdomain/​zero/​1.​0/​) applies to the data made available in this article, unless otherwise stated.

Competing interests

The authors declare that they have no competing interests.

Authors’ contributions

PAD-V conducted the data collection and analyses. PAD-V, PB and AJV, contributed to the writing of the manuscript. All authors read and approved the final manuscript.
Anhänge

Additional files

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Metadaten
Titel
Global epidemiology of type 1 diabetes in young adults and adults: a systematic review
verfasst von
Paula A Diaz-Valencia
Pierre Bougnères
Alain-Jacques Valleron
Publikationsdatum
01.12.2015
Verlag
BioMed Central
Erschienen in
BMC Public Health / Ausgabe 1/2015
Elektronische ISSN: 1471-2458
DOI
https://doi.org/10.1186/s12889-015-1591-y

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