Epidemiology of childhood type I diabetes in Crete, 1990–2001

D Mamoulakis, E Galanakis, S Bicouvarakis, E Paraskakis and S Sbyrakis

Department of Paediatrics, University of Crete, Heraklion, Greece

Mamoulakis D, Galanakis E, Bicouvarakis S, Paraskakis E, Sbyrakis S. Epidemiology of childhoodtype I diabetes in Crete, 1990–2001. Acta Pædiatr 2003; 92: 737–739. Stockholm. ISSN 0803-5253

Aim: To study the epidemiological patterns of childhood-onset type I diabetes in Crete, Greece.Methods: The incidence (new cases per 100000 per year) from 1990 to 2001 was determined inthe population of Crete �14 y of age. Results: A total of 89 cases was ascertained. Thestandardized annual incidence rate was 6.1 per 100000 population [95% confidence interval (95%CI) 4.9–7.5]. Incidence rates were higher in children 10–14 y of age, boys and residents of urbanareas (6.8, 6.7 and 6.6 per 100000, respectively). Incidence rates were higher [relative risk (RR)1.46, 95% CI 0.956–2.24] during the 6 y period 1996–2001 (7.2, 95% CI 5.4–9.4) than during the6 y period 1990–1995 (4.9, 95% CI 3.4–6.9). This increase was more prominent in residents ofurban areas and 10–14-y-old children.

Conclusions: Although an increase was noted during the period 1990–2001, the childhood type Idiabetes incidence rates in Crete remain among the lowest both in Europe and in theMediterranean islands.

Key words: Crete, diabetes epidemiology, Greece, type I diabetes

E Galanakis, Department of Paediatrics, University of Crete, POB 1393, GR-71500 Heraklion,Greece (Tel. �30 2810 392 012, fax. �30 2810 392 827, e-mail. egalanak@med.uoc.gr)

A very large range of global variation in the incidenceof type I diabetes has been documented and a rapidincrease has been recently observed in most populations(1–3). The incidence of type I diabetes in children incertain regions of Greece has already been reported (3–6); however, it has not been studied for the island ofCrete in particular. Crete is located in the south-easterncorner of the European continent and has not beenincluded in the EURODIAB or DiaMond studies (2, 3).The purpose of this study was to provide informationabout the recent epidemiology of type I diabetes inCrete, among children aged 0–14 y, over a period of12 y.

Population and methodsThe population of Crete is quite stable and geneticallyhomogeneous, and numbers 601159 inhabitants (2001census), 42% of whom are urbanized. The island is notheavily industrialized and economy is largely based onagriculture and tourism. Crete is well known for thetraditional Mediterranean type of diet, which has beenrelated to low rates of coronary heart disease and cancermortality (7).

The study included all children aged 0–14 y whowere diagnosed as having type I diabetes during the 12 yperiod 1 January 1990 to 31 December 2001. Capture–recapture methodology, which assumes the availability

of independent primary and secondary sources ofascertainment, was used (1, 3). Data were primarilycollected from the inpatients’ medical notes and fromthe register of the Paediatric Diabetology Clinic at theUniversity Hospital of Heraklion. This is the only clinicon the island of Crete. Secondary sources includedcentres such as the “P. and A. Kyriakou” AthensChildren’s Hospital Diabetic Clinic, where Cretanchildren with diabetes may have been cared for. Creteis a well-known resort, accommodating significantpopulations of children on holiday; therefore patientswho were resident in Crete for �12 mo before the onsetof symptoms were excluded from this incidence study(6). Type I diabetes was defined on the basis of a clinicaldiagnosis (2). The date of the first insulin injection wasdefined as the date of diagnosis.

Incidence rates were calculated as the incidence percalendar year and 100000 individuals at risk, usingcensus data from 1991 and 2001 with extrapolation forthe intermediate years, as obtained by the NationalStatistics Service of Greece. Standardized rates werecalculated, assuming a standard population with age andgender groups of equal sizes. Incidence rates werefurther calculated for age intervals (0–4, 5–9 and 10–14 y), for each gender and for the place of residence.The place of residence was defined as urban for townsof more than 10000 population and rural for settlementsof less than 10000. Owing to the relative rarity of type Idiabetes and the small number of cases, 95% confidence

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DOI 10.1080/08035250310002588

intervals (95% CI) were estimated using the Poissondistribution (8). Relative risks (RR) and 95% CI wereused to investigate differences in incidence ratesbetween populations (8).

ResultsA total of 89 cases (50M, 39F) was recorded during theregistration period. Two cases were ascertained by thesecondary sources and the completeness of ascertain-ment was estimated at 97.8%. The standardizedincidence rate was 6.1 per 100000 children per year.The incidence rates according to age, gender andresidence are shown in Table 1. An increased incidencerate was observed in the eastern part of Crete comparedwith the western part (7.0 and 4.5, respectively; RR1.55, 95% CI 0.971–2.48). A seasonal variation wasobserved, with more cases occurring during the 6 moperiod October to March than during April to Septem-ber (60% and 40% cases, respectively). None of the 89children had affected siblings or first-degree relatives.

In almost all groups incidence rates were higherduring 1996–2001 than during 1990–1995 (Table 2).This increase was more prominent in urban areas (RR

2.26, 95% CI 1.18–4.32) and 10–14-y-old children (RR1.97, 95% CI 0.992–3.93). By contrast, no increase wasnoted in 0–4-y-old children (RR 1.05, 95% CI 0.428–2.59) or in rural areas (RR 0.991, 95% CI 0.552–1.78).

DiscussionType I diabetes is believed to be the consequence of animmune destruction of pancreatic �-cells in geneticallysusceptible individuals exposed to environmental riskfactors (3). Incidence is considered as very low, low,intermediate, high and very high at the rates of �1,1–4.99, 5–9.99, 10–19.99 and �20 per 100000 per year,respectively (1). The global variation in the incidencehas a large range and differences greater than 350-foldamong different populations have been documented (1).In Europe, a greater than 10-fold range has beenreported (3–4), with rates varying from 3.2 in theFormer Yugoslav Republic of Macedonia to 40.2 inregions of Finland (3). Incidence rates are generallyhigh in northern and north-western Europe and low incentral, southern and eastern Europe (3). The causesbehind these differences, even between borderingcountries, are still not explained. Ethnic factors havebeen considered. It has thus been observed that inGermany the incidence is lower for children who are notof German descent than for German children (9),whereas other studies have shown considerable differ-ences in rates between related populations (1). How-ever, the recent rapid increase in Europe and world-wide has been attributed to changes in environmentalfactors (2, 10).

The incidence of type I diabetes in Greece is amongthe lowest in Europe (3–5). In Crete the incidence islower than in the Athens area, close to that observed innorthern regions of Greece (9.5 and 6.2, respectively)(3), and remarkably lower than in Cyprus, Sicily andMalta (10.5, 11.4 and 14.7, respectively) (2, 3, 11, 12).Sardinia is well known for the very high rate of 36.6 per100000 (3). The recent rise in incidence rates docu-mented in Crete is a general observation for the whole

Table 1. Incidence (as new cases per 100000 per year) of type Idiabetes in children �14 y of age in Crete, 1990–2001.

Children’s groupCases/person-years

at riskIncidence rates

(95% CI)

All children(standardized ratea)

89/1459728 6.1 (4.9–7.5)

Boys 50/750684 6.7 (4.9–8.8)Girls 39/709044 5.5 (3.9–7.5)0–4 y old 19/430008 4.4 (2.7–6.9)5–9 y old 33/489324 6.7 (4.6–9.5)10–14 y old 37/540396 6.8 (4.8–9.4)Rural residence 45/794880 5.7 (4.1–7.6)Urban residence 44/664848 6.6 (4.8–8.9)

a The standard population assumes equal sizes of age groups 0–5, 5–9and 10–14 y for boys and girls.

95% CI: 95% confidence interval.

Table 2. Incidence (as new cases per 100000 per year) of type I diabetes in children �14 y of age in Crete, 1990–1995 and 1996–2001.

Children’s group

1990–1995 1996–2001

Cases/person-years at risk Incidence rates (95% CI) Cases/person-years at risk Incidence rates (95% CI)

All children (standardized ratea) 35/710322 4.9 (3.4–6.9) 54/749406 7.2 (5.4–9.4)Boys 20/365292 5.5 (3.3–8.5) 30/385392 7.8 (5.3–11.1)Girls 15/345030 4.3 (2.4–7.2) 24/364014 6.6 (4.2–9.8)0–4 y old 9/209250 4.3 (2.0–8.2) 10/220758 4.5 (2.2–8.3)5–9 y old 14/238110 5.9 (3.2–9.9) 19/251214 7.6 (4.6–11.8)10–14 y old 12/262962 4.6 (2.4–8.0) 25/277434 9.0 (5.8–13.3)Rural residence 22/386796 5.7 (3.6–8.6) 23/408084 5.6 (3.6–8.5)Urban residence 13/323526 4.0 (2.1–6.9) 31/341322 9.1 (6.2–12.9)

a The standard population assumes equal sizes of age groups 0–5, 5–9 and 10–14 y for boys and girls.95% CI: 95% confidence interval.

738 D Mamoulakis et al. ACTA PÆDIATR 92 (2003)

of Europe (3). However, in Athens a relatively stableincidence at about 9–10 per 100000 children annuallyhas been confirmed for the 1990s (6).

The incidence as a rule increases with age, with thehighest rates among children 10–14 y of age (1). A rapidrate of increase in children aged under 5 y has beendocumented for other areas of Europe (3, 10), but thiswas not observed in the present study. Increasedincidence rates in boys have been reported in manycountries (1, 4, 6), but not by all studies from Greeceand Cyprus (5, 11). Increased incidence rates in urbanpopulations have already been reported (4, 5) and wereconfirmed by the present study.

For the rather small population of Crete, a studyperiod of 12 y is too short to allow a proper investiga-tion of trends in incidence. Nevertheless, the geogra-phical location of the island and the genetichomogeneity of the population provide several oppor-tunities for descriptive epidemiological studies. Chil-dren in Crete have an intermediate incidence of type Idiabetes which, despite the recent increase, remainslower than that observed both in other regions of Greeceand Europe and in the other Mediterranean islands.

Acknowledgements.—We thank Ieroniki Kanakaraki, HeraklionUniversity Hospital, and Ioanna Thymeli, “P. and A. Kyriakou”Athens Children’s Hospital, for their contribution in recording thepatients.

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Received Sept. 27, 2002; revisions received Jan. 31, 2003; acceptedFeb. 11, 2003

ACTA PÆDIATR 92 (2003) Childhood type I diabetes in Crete 739