Diabetologia

, Volume 52, Issue 12, pp 2531–2535

The incidence of type 1 diabetes is increasing in both children and young adults in Northern Italy: 1984–2004 temporal trends

  • G. Bruno
  • G. Novelli
  • F. Panero
  • M. Perotto
  • F. Monasterolo
  • G. Bona
  • A. Perino
  • I. Rabbone
  • P. Cavallo-Perin
  • F. Cerutti
  • Piedmont Study Group for Diabetes Epidemiology
Short Communication

DOI: 10.1007/s00125-009-1538-x

Cite this article as:
Bruno, G., Novelli, G., Panero, F. et al. Diabetologia (2009) 52: 2531. doi:10.1007/s00125-009-1538-x
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Abstract

Aims/hypothesis

A shift towards younger age at onset of diabetes in susceptible people has been suggested as a possible explanation for the increasing temporal trend in incidence of type 1 diabetes. We aimed to test this hypothesis by assessing trends in incidence rates in the period 19842004 in children and young adults in Northern Italy.

Methods

The study bases were: (1) children resident in the Province of Turin in the period 19842004 and in the remaining areas of the Piedmont Region in the period 19902004; and (2) young adults (1529 years) resident in the Province of Turin in the period 19842003. Temporal trends in rates were analysed using Poisson regression models.

Results

A total of 1,773 incident cases were identified. Overall incidence rates/100,000 person-years in the age groups 014 and 1529 years were 11.3 (95% CI 10.712.0) and 7.1 (95% CI 6.67.7), respectively, with sex differences among young adults only (incidence rate ratio [IRR] in males vs females 1.41 [95% CI 1.201.64]). Average annual increases in incidence rates were similar in children and young adults at 3.3% (95% CI 2.54.1). Compared with the period 198489, in 20002004 a 60% higher risk was found in both age 014 years (IRR 1.60, 95% CI 1.311.95) and 1529 years (IRR 1.57, 95% CI 1.261.96) groups. The Poisson modelling showed no interaction between calendar period and age at onset.

Conclusions/interpretation

Incidence of type 1 diabetes in Northern Italy is increasing over time in both children and young adults, not supporting the hypothesis of a shift towards younger age as the main explanation for the increasing temporal trend in children.

Keywords

Adult-onset diabetesIncidenceItalyRegistrySurveyTemporal trend

Abbreviations

IRR

Incidence rate ratio

LR

Likelihood ratio

Introduction

Geographical and temporal variations in the incidence of type 1 diabetes have been pointed out worldwide, with recent data from Northern European registries showing that risk is increasing even faster than before, particularly in Finland [13]. A shift towards younger age at onset in susceptible individuals rather than a true lifetime increasing risk of the disease has been suggested by the few studies that extended the recruitment of incident cases up to adults [4, 5].

The first Italian population-based registry of type 1 diabetes was set up in 1984 in Turin, Northern Italy, to monitor the incidence rate of the disease up to age 29 years [6]. In this report, we aimed to extend the study base of our registry over both space and time, to examine incidence trends of the disease in both children (014 years) and young adults (1529 years) in the period 19842004.

Methods

The study bases of this report were: (1) children 014 years of age resident in the Province of Turin (number of inhabitants 2,165,619 at the 2001 census) in the period 19842004 and in the remaining areas of the Piedmont Region (number of inhabitants 2,049,058) in the period 19902004; and (2) young adults (1529 years) resident in the Province of Turin in the period 19842003. Incident cases of type 1 diabetes arising in the study period were identified through the following sources of ascertainment: (1) diabetes clinics from public and private hospitals, to which diabetic patients are referred after diagnosis, (primary source); and (2) files of all patients who had obtained exemption from payment for drugs, syringes and glucose-monitoring strips because of a diagnosis of diabetes mellitus (secondary source). The estimated completeness of ascertainment was assessed by using the two-sample capture–recapture method. A diagnosis of type 1 diabetes was based on permanent insulin treatment within 6 months of diagnosis, fasting C-peptide levels ≤0.20 nmol/l or positivity for antibodies to islet cells (ICA) or GADA. Denominators of incidence rates were intercensual estimates of residents in the Piedmont Region and its eight provinces (Turin, Alessandria, Asti, Biella, Cuneo, Novara, Verbania and Vercelli). Incidence rates for the periods 19841989, 19901994, 19951999 and 20002004 were compared by computing incidence rate ratios (IRRs) and 95% CIs.

Time trends in incidence rates were modelled by Poisson regression modelling. Sex, age (six 5 year age groups), province (n = 8) and calendar period (19841989, 19901994, 19951999 and 20002004) were independent variables. Models were compared by the likelihood ratio (LR) test. We also estimated time trends after stratification by age group to assess if they differed significantly. Age-period cohort analysis was also performed, updating previous data from the Province of Turin, as previously described [6]. All statistical analyses were performed using STATA, release 10.0 (Stata, College Station, TX, USA).

Results

In the period 19842004, 1,773 incident cases of type 1 diabetes aged 029 years were identified in the study base, giving an overall incident rate/100,000 person-years of 9.3 (95% CI 8.99.7), with an high estimated completeness of ascertainment over calendar periods 19841989, 19901994, 19951999 and 20002004, in the age group 014 years (99%, 97%, 99% and 99%) and in the age group 1529 years (95%, 99%, 98% and 97%). Rates are based on 1,123 children identified in the period 19842004 and on 650 young adults identified in the period 19842003.

Overall incidence rates/100,000 person-years were 11.3 (95% CI 10.712.0) in the age group 014 years and 7.1 (95% CI 6.67.7) in the age group 1529 years. Rates/100,000 person-years in the age groups 04, 59 and 1014 years were 8.3 (95% CI 7.39.4), 11.7 (95% CI 10-6-13.0) and 13.6 (95% CI 12.414.8), respectively; indeed, the majority of incident cases were identified in the pubertal age (IRR 1.64, 95% CI 1.411.91, with respect to the age group 04 years, p < 0.0001). Incidence rates by age at onset and cumulative incidence by calendar period are shown in the Electronic supplementary material (ESM) Figs 1 and 2.

The risk of childhood diabetes was similar in males and females: 11.8/100,000 (95% CI 10.912.8) vs 10.8/100,000 (95% CI 9.911.8), respectively. In contrast, a 40% higher risk in males than in females was evident among young adults: 8.2/100,000 (95% CI 7.19.1) vs 5.9/100,000 (95% CI 5.26.6), giving an IRR of 1.41 (95% CI 1.201.65).

The incidence rate increased over the period 19842004, with an average annual increase of 3.3% (95% CI 2.54.1), slightly higher in age 014 years (4.3%, 95% CI 2.06.6) than in age 1529 years (2.8%, 95% CI 1.04.6). Indeed, the largest annual increase was seen in the 04 year age group (4.3%, 95% CI 2.06.6); corresponding values in the age groups 59 and 1014 years were 2.8% (95% CI 1.04.6) and 2.7% (95% CI 1.24.3%). However, differences in annual increases among age groups did not reach statistical significance.

Incidence rates/100,000 person-years separately for age group, calendar period and area are shown in Table 1. In the last time period, a 60% increased risk with respect to the period 19841989 was found in both age 014 years (IRR 1.60, 95% CI 1.311.95) and 1529 years (IRR 1.57, 95% CI 1.261.96). Point estimate of risks were twofold higher in the latter time period in the age group 04 years (IRR 1.92, 95% CI 1.213.05) and in the age group 59 years (IRR 1.90, 95% CI 1.352.68), but differences were not statistically significant. Examining incidence rates in children resident in the whole Piedmont Region in the period 19902004, the amount of the increase in the period 20002004 was 33% with respect to 19901994.
Table 1

Incidence rates/100,000 person-years of type 1 diabetes in the Piedmont Region, by age group and calendar period

Location/period

Age 0–4 years

Age 5–9 years

Age 10–14 years

Age 0–14 years

Age 15–29 yearsa

n

Rate

IRR

n

Rate

IRR

n

Rate

IRR

n

Rate

IRR

n

Rate

IRR

Province of Turin

1984–1989

29

5.3 (3.7–7.6)

1.00

58

8.8 (6.8–11.4)

1.00

106

12.0 (9.7–14.5)

1.00

193

9.4 (8.0–10.6)

1.00

187

6.0 (5.2–7.0)

1.00

1990–1994

43

9.8 (7.3–13.2)

1.86 (1.16–2.98)

49

10.9 (8.2–14.4)

1.23 (0.84–1.80)

61

11.7 (9.1–15.0)

0.97 (0.71–1.33)

153

10.8 (9.2–12.7)

1.17 (0.95–1.45)

173

6.9 (6.0–8.0)

1.14 (0.93–1.40)

1995–1999

28

6.3 (4.4–9.2)

1.20 (0.72–2.03)

63

14.2 (11.1–18.2)

1.61 (1.12–2.29)

57

12.5 (9.6–16.2)

1.04 (0.75–1.43)

148

11.0 (9.4–13.0)

1.19 (0.96–1.48)

154

7.2 (6.2–.8.5)

1.20 (0.97–1.48)

2000–2004

47

10.1 (7.6–13.4)

1.92 (1.21–3.05)

74

16.7 (13.3–21.0)

1.90 (1.35–2.68)

79

17.7 (14.2–22.0)

1.47 (1.10–1.97)

200

14.8 (12.9–17.0)

1.60 (1.31–1.95)

136

9.5 (8.0–11.2)

1.57 (1.26–1.96)

Piedmont Regionb

1990–1994

70

8.4 (6.7–10.7)

1.00

95

11.2 (9.1–13.7)

1.00

118

12.0 (10.0–14.4)

1.00

283

10.6 (9.5–11.9)

1.00

   

1995–1999

56

6.7 (5.1–8.7)

0.79 (0.56–1.12)

112

13.2 (11.0–15.9)

1.19 (0.90–1.55)

111

12.7 (10.6–15.4)

1.06 (0.82–1.38)

279

10.9 (9.7–12.3)

1.03 (0.87–1.21)

   

2000–2004

102

11.6 (9.5–14.0)

1.37 (1.01–1.85)

112

13.1 (10.9–15.8)

1.17 (0.89–1.54)

154

17.8 (15.2–20.9)

1.49 (1.17–1.89)

368

14.1 (12.8–15.7)

1.33 (1.14–1.55)

   

aAge at onset 15–29 years in the period 1984–2003

bEight provinces, including the province of Turin

Poisson regression analysis (Table 2) showed a linearly increasing trend over time, independently of age, sex and geographical area (model 5). The Poisson modelling showed no evidence of interaction between calendar period and either sex (model 6) or age (model 7), whereas interaction between age and sex was significant (model 8; p = 0.01); in this final model, the linearly increasing trend was 3.0% per year (95% CI 2.13.8).
Table 2

Result of Poisson regression model fitting for type 1 diabetes in the Piedmont Region, 1984–2004

Model/variables

Deviance

df

LR χ2 for the last term

df

p value

1 Age

974.73

870

143.5

5

<0.0001

2 Age + sex

960.20

869

14.1

1

0.0002

3 Age + sex + year

913.72

868

46.9

1

<0.0001

4 Age + sex + period

911.68

866

48.95a

3a

<0.0001

5 Age + sex + year + province

901.50

861

12.23b

7b

0.09

6 Age + sex + year + province + age2 × period

897.22

856

4.27

5

0.52

7 Age + sex + year + province + sex × period

895.06

856

6.44c

5c

0.27

8 Age + sex + year + province + age2 × sex

895.02

860

6.48c

1c

0.01

Age is entered in models as six age groups (0–4, 5–9, 10–14, 15–19, 20–24, 25–29 years)

Age2 is entered in models as age 0–14 and 15–29 years

Year is entered in models as a linear term of year at onset

Period is entered in models as four calendar periods of onset (1984–1989, 1990–1994, 1995–1999, 2000–2004)

Province is entered in models as eight provinces (Turin, Alessandria, Asti, Biella, Cuneo, Novara, Verbania, Vercelli)

aWith respect to model 2

bWith respect to model 3

cWith respect to model 5

Age-period cohort analysis (ESM Tables 1 and 2) showed a linearly increasing trend (drift), not interpretable on a statistical basis as related to calendar period or cohort effects, which corresponds to an IRR of 1.17 (1.131.21; p < 0.0001) for each age span of 5 years.

Discussion

Our study shows that the incidence rate of type 1 diabetes in Northern Italy has markedly increased over the monitored time period of 20 years. Compared with the period 19841989, the risk had increased by 60% in the period 20002004. The amount of the annual increase (3.3%) is similar to that found in other European areas. The new finding of our analyses is that the increasing temporal trend is similarly evident in children and young adults. Therefore, our data are not consistent with the hypothesis of a shift towards a younger age at onset in susceptible people as a possible explanation for the temporal increase of childhood diabetes, as suggested by some [4, 5] but not all registries [7, 8]. Our data expand current knowledge on this issue to the Mediterranean population, suggesting that ubiquitous environmental determinants affecting both children and young adults born in the last three decades are involved in this phenomenon.

The identification of widespread determinants of unknown origin is a difficult task for epidemiological research. Although the increasing temporal trend seems to be even faster in more recent years in Germany, Austria and Finland, no spike in incidence has been identified in these countries [13]. As recently pointed out, viral infections could be involved in the pathogenesis of diabetes by inhibiting rather than inducing a diabetogenic response [9]. Studies have proposed that the decreasing early life exposure to infectious diseases, which typically occurred over the past three decades in developed countries, could be involved in the increasing temporal trend of immune-mediated disorders, multiple sclerosis, type 1 diabetes and inflammatory bowel diseases [10]. All of these diseases, by contrast, are uncommon in developing countries. Further epidemiological and immunological studies, however, are needed to test the so-called ‘hygiene hypothesis’.

Consistently with previous age-period cohort analysis of the registry of the Province of Turin in the period 19841996 [6], in this report we showed a linearly increasing trend, which could be attributed to either a period or a cohort effect. Our data are based on the extension of our registry to residents in the whole Piedmont Region, thus allowing a description of risk of type 1 diabetes on a population of almost 5 million inhabitants over a 20 year time period. The long time span examined in this report, the almost complete case ascertainment over all the study period and the recruitment of incident cases arising both in childhood and in adulthood with accurate methodology are strengths of the present report. Monitoring incidence of type 1 diabetes through the registries is both a time- and resource-consuming activity. However, population-based data are still needed, both to suggest hypotheses on the determinants of the disease and to provide data on its global burden for healthcare planners. Since a doubling in the number of incident cases can be expected every three decades, both quantity and quality of care provided to young people with diabetes should be markedly improved over the coming years.

In conclusion, incidence of type 1 diabetes in Northern Italy is increasing over time in both children and young adults. Our findings do not support the hypothesis of a shift towards younger age at onset as the main explanation for the increasing temporal trend of the disease in children.

Acknowledgements

This study was supported by grants from the Piedmont Region (Ricerca Sanitaria Finalizzata 2007 and 2008) and from the University of Turin.

Duality of interest

The authors declare that there is no duality of interest associated with this manuscript.

Supplementary material

125_2009_1538_MOESM2_ESM.pdf (18 kb)
ESM Table 1(PDF 18 kb)
125_2009_1538_MOESM3_ESM.pdf (10 kb)
ESM Table 2(PDF 10 kb)
125_2009_1538_MOESM4_ESM.pdf (25 kb)
ESM Fig. 1(PDF 25 kb)
125_2009_1538_MOESM5_ESM.pdf (16 kb)
ESM Fig. 2(PDF 16 kb)

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • G. Bruno
    • 1
  • G. Novelli
    • 1
  • F. Panero
    • 1
  • M. Perotto
    • 1
  • F. Monasterolo
    • 1
  • G. Bona
    • 2
  • A. Perino
    • 2
  • I. Rabbone
    • 3
  • P. Cavallo-Perin
    • 1
  • F. Cerutti
    • 3
  • Piedmont Study Group for Diabetes Epidemiology
  1. 1.Department of Internal MedicineUniversity of TurinTurinItaly
  2. 2.Department of PediatricsUniversity of NovaraNovaraItaly
  3. 3.Department of PediatricsUniversity of TurinTurinItaly