Global epidemiology of type 1 diabetes in young adults and adults: a systematic review (original) (raw)

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

CRD42012002369.

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.

Keywords: Type 1 diabetes, Systematic review, Adults, Incidence, Epidemiology

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.

Figure 1.

Figure 1

PRISMA Flow diagram bibliographic search strategies. * Kumar P, et al. Indian Med Assoc. 2008;106(11):708–711. ** The article: Radosevic B, et al. Pediatr Diabetes. 2013;14(4):273–4 gives information from two countries: 1) Bosnia and Herzegovina: Republic of Srpska and 2) Slovenia, Nationwide.

Data collection

For each study, the following information was extracted:

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

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).

Figure 2.

Figure 2

Age variation of incidence from childhood to adult age. On this figure, the adult estimates of incidence were taken from the 14 reports of the systematic review using the autoantibodies/C-peptide as diagnostic criteria. Full lines correspond to articles from which both child as well as adult information could be retrieved. The dotted lines are those for which the child information was searched in the same country as in the adult paper, but was from a different paper (see Additional file 3 for details on this literature search). The corresponding countries are shown as: BE1: Belgium (2007) [30]; BE2: Belgium (2002) [31]; BE3: Belgium (1997) [32]; DK: Denmark [34]; ES1: Spain, Catalonia [54]; ES2: Spain, Navarra (2014) [56]; ES3: Spain, Navarra (2013) [57]; FI: Finland [35]; IR: Iran (Islamic Republic of) [15]; IT: Italy [45,46]; SE: Sweden [63], TW: Taiwan [81]; US: United States of America [74].

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).

Figure 3.

Figure 3

Geographical correlation of T1D incidence between individuals aged 0–14 years and adults. Studies using autoantibodies/C-Peptide for T1D case definition are identified by Red diamonds. The corresponding countries are shown as: BE1: Belgium (2007) [30]; BE2: Belgium (2002) [31]; BE3: Belgium (1997) [32]; DK: Denmark [34]; ES1: Spain, Catalonia [54]; ES2: Spain, Navarra (2014) [56]; ES3: Spain, Navarra (2013) [57]; FI: Finland [35]; IR: Iran (Islamic Republic of) [15]; IT: Italy [45,46]; SE: Sweden [63], TW: Taiwan [81]; US: United States of America [74]. Sp. Cor: Spearman correlation.

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.

Additional files

Footnotes

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.

Contributor Information

Paula A Diaz-Valencia, Email: paula.diaz@inserm.fr.

Pierre Bougnères, Email: pierre.bougneres@inserm.fr.

Alain-Jacques Valleron, Email: alain-jacques.valleron@inserm.fr.

References