**3.2. Changes over the last years**

A global rise in the incidence of type 1 diabetes in children and adolescents has been report‐ ed over the past decades (Onkamo, Vaananen et al. 1999; Karvonen, Viik-Kajander et al. 2000; Soltesz 2003; Aamodt, Stene et al. 2007; Soltesz, Patterson et al. 2007). The world-wide annual increment of type 1 diabetes has already been summarized in the work of Onkamo, Vaananen et al. (1999). They found a statistically significant increase of incidence in 65% (24/37) of the examined populations. A non-statistically significant upward tendency was seen in another 12 populations, while a statistically significant decrease of type 1 diabetes incidence was not found. The global trend of the increase in the incidence of type 1 diabetes was 3.0% per year (95% CI 2.59-3.33; p < 0.001; Onkamo, Vaananen et al. 1999).

ter also found the average annual increase of incidence to be significantly higher in boys

The Epidemiology of Type 1 Diabetes Mellitus

http://dx.doi.org/10.5772/52893

9

Taken together the reported studies suggest no sex-dependent differences in the incidence of type 1 diabetes. Type 1 diabetes can be assumed to be the only major organ-specific auto‐ immune disease not to show a strong female bias. The overall sex ratio is roughly equal in children diagnosed under the age of 15 years (Gale and Gillespie 2001). After the age of pub‐ erty, males are more frequently affected than females (Nystrom, Dahlquist et al. 1992).

The following sections are intended to answer two questions: 1) does the incidence of type 1 diabetes differ between distinct age groups, and 2) what changes of the incidence of type 1

The incidence of type 1 diabetes shows an age-dependent pattern. It was reported to be sig‐ nificantly lower in the 0– to 4-year-old group than in the other groups (Bizzarri, Patera et al. 2010). Many studies from different countries reported an increase of the incidence with in‐ creasing age. The highest incidences were found in the 10 to 14-year-old age group (Karvo‐ nen, Viik-Kajander et al. 2000; Michaelis et al., 1993; Neu, Ehehalt et al. 2001; Taplin, Craig et

The increasing incidence of type 1 diabetes is evident. Although some groups found no age-de‐ pendent differences in the annual increment of type 1 diabetes incidence (Taplin, Craig et al. 2005; Svensson, Lyngaae-Jorgensen et al. 2009; Abduljabbar, Aljubeh et al. 2010), the majority of the published studies reported different increments of incidence after stratifying children and youths into different age groups: Michealis et. al (1993) found an increment of incidence of about 12.6% in 0- to 9-year-old children, in 10- to 19-year-old children the increment was 3.8%. Similar results were reported by other German groups (Neu, Ehehalt et al. 2001; Ehehalt, Blumenstock et al. 2008): the relative increment of type 1 diabetes incidence was 5.7% per year in 0- to 4-year-old children, the other age groups showed smaller increments. The incidence of childhood-onset type 1 diabetes in Estonian children under 15 years of age increased annually by an average of 3.3% with the most rapid annual increase (9.3%) occurring in the youngest age group (Teeaar, Liivak et al. 2010). The EURODIAB register repeatedly confirmed that in Europe the annual in‐ crease of incidence is higher in younger children (0 to 4 years of age; Green and Patterson 2001;

When discussing seasonal differences in the epidemiology of type 1 diabetes, two different aspects must be mentioned: 1) different frequency of type 1 diabetes regarding the season of

birth, and 2) the changing onset or diagnosis of type 1 diabetes through the year.

**3.4. Age-dependent differences of type 1 diabetes mellitus incidence**

diabetes within these age groups occurred over the last years.

*3.4.1. The age-dependent pattern of type 1 diabetes mellitus incidence*

**3.5. Seasonal differences of type 1 diabetes mellitus incidence**

al. 2005; Samardzic, Marinkovic et al. 2010).

Patterson, Dahlquist et al. 2009).

*3.4.2. The increase of incidence in different age groups*

(3.8% vs. 1.9%, p = 0.046).

The United States stood apart from other nations in reporting a stable incidence of child‐ hood type 1 diabetes in the 1970s through the 1990s (Vehik and Dabelea 2010). The multi‐ center Search for Diabetes in Youth Study (SEARCH) reported that the 2002 to 2005 incidence of type 1 diabetes in non-Hispanic White younger than 14 years of age was 27.5/100,000 per year (Bell, Mayer-Davis et al. 2009). This exceeded the incidence predicted for 2010 by earlier data from Allegheny County, Pennsylvania (Dokheel 1993). A similar de‐ velopment was noticed by estimated data from Colorado (Vehik and Dabelea 2010).

For Europe, data from the EURODIAB-register suggest an annual increment of incidence of about 0.6-15% (see Table 2 for details; Patterson, Dahlquist et al. 2009). Earlier data regard‐ ing type 1 diabetes incidence from all 36 EURODIAB-centers were published by Green and Patterson (2001).

Regarding the strong differences in the annual increase in the incidence of type 1 diabetes between the countries, it must be mentioned that, besides the geographic differences, the in‐ cidence trend was found not to be continuously linear. Furthermore, the incidence trend in‐ creases exponentially. Predictions made by Onkamo et al. for the incidence rates in 2010 pointed to large increases, but, in retrospect, were too conservative, especially regarding younger children (Knip 2012).

#### **3.3. Sex-dependent differences of type 1 diabetes mellitus incidence**

Despite matched-pair investigations suggested that for some early childhood risk factors the odds ratio in boys were different from those in girls (Svensson, Carstensen et al. 2005), most of the published studies reported no significant difference between the type 1 diabetes inci‐ dence in boys and girls (Shaltout, Qabazard et al. 1995; Abellana, Ascaso et al. 2009; Svens‐ son, Lyngaae-Jorgensen et al. 2009; Samardzic, Marinkovic et al. 2010; Teeaar, Liivak et al. 2010). Other groups found small and thereby not relevant sex-related differences only for subgroups (Shaltout, Qabazard et al. 1995). A sex-related difference in incidence was found only in the 10- to 14-year age group with a significantly higher incidence in boys (18.77 vs. 14.7/100,000/year, p = 0.015; Bizzarri, Patera et al. 2010). However, a statistically significantly higher incidence in girls was reported by a Libyan (Kadiki and Roaeid 2002), a Thai (Pana‐ monta, Thamjaroen et al. 2011), and an Australian group (Taplin, Craig et al. 2005). The lat‐ ter also found the average annual increase of incidence to be significantly higher in boys (3.8% vs. 1.9%, p = 0.046).

Taken together the reported studies suggest no sex-dependent differences in the incidence of type 1 diabetes. Type 1 diabetes can be assumed to be the only major organ-specific auto‐ immune disease not to show a strong female bias. The overall sex ratio is roughly equal in children diagnosed under the age of 15 years (Gale and Gillespie 2001). After the age of pub‐ erty, males are more frequently affected than females (Nystrom, Dahlquist et al. 1992).

### **3.4. Age-dependent differences of type 1 diabetes mellitus incidence**

The following sections are intended to answer two questions: 1) does the incidence of type 1 diabetes differ between distinct age groups, and 2) what changes of the incidence of type 1 diabetes within these age groups occurred over the last years.

#### *3.4.1. The age-dependent pattern of type 1 diabetes mellitus incidence*

The incidence of type 1 diabetes shows an age-dependent pattern. It was reported to be sig‐ nificantly lower in the 0– to 4-year-old group than in the other groups (Bizzarri, Patera et al. 2010). Many studies from different countries reported an increase of the incidence with in‐ creasing age. The highest incidences were found in the 10 to 14-year-old age group (Karvo‐ nen, Viik-Kajander et al. 2000; Michaelis et al., 1993; Neu, Ehehalt et al. 2001; Taplin, Craig et al. 2005; Samardzic, Marinkovic et al. 2010).

#### *3.4.2. The increase of incidence in different age groups*

**3.2. Changes over the last years**

8 Type 1 Diabetes

Patterson (2001).

younger children (Knip 2012).

A global rise in the incidence of type 1 diabetes in children and adolescents has been report‐ ed over the past decades (Onkamo, Vaananen et al. 1999; Karvonen, Viik-Kajander et al. 2000; Soltesz 2003; Aamodt, Stene et al. 2007; Soltesz, Patterson et al. 2007). The world-wide annual increment of type 1 diabetes has already been summarized in the work of Onkamo, Vaananen et al. (1999). They found a statistically significant increase of incidence in 65% (24/37) of the examined populations. A non-statistically significant upward tendency was seen in another 12 populations, while a statistically significant decrease of type 1 diabetes incidence was not found. The global trend of the increase in the incidence of type 1 diabetes

The United States stood apart from other nations in reporting a stable incidence of child‐ hood type 1 diabetes in the 1970s through the 1990s (Vehik and Dabelea 2010). The multi‐ center Search for Diabetes in Youth Study (SEARCH) reported that the 2002 to 2005 incidence of type 1 diabetes in non-Hispanic White younger than 14 years of age was 27.5/100,000 per year (Bell, Mayer-Davis et al. 2009). This exceeded the incidence predicted for 2010 by earlier data from Allegheny County, Pennsylvania (Dokheel 1993). A similar de‐

For Europe, data from the EURODIAB-register suggest an annual increment of incidence of about 0.6-15% (see Table 2 for details; Patterson, Dahlquist et al. 2009). Earlier data regard‐ ing type 1 diabetes incidence from all 36 EURODIAB-centers were published by Green and

Regarding the strong differences in the annual increase in the incidence of type 1 diabetes between the countries, it must be mentioned that, besides the geographic differences, the in‐ cidence trend was found not to be continuously linear. Furthermore, the incidence trend in‐ creases exponentially. Predictions made by Onkamo et al. for the incidence rates in 2010 pointed to large increases, but, in retrospect, were too conservative, especially regarding

Despite matched-pair investigations suggested that for some early childhood risk factors the odds ratio in boys were different from those in girls (Svensson, Carstensen et al. 2005), most of the published studies reported no significant difference between the type 1 diabetes inci‐ dence in boys and girls (Shaltout, Qabazard et al. 1995; Abellana, Ascaso et al. 2009; Svens‐ son, Lyngaae-Jorgensen et al. 2009; Samardzic, Marinkovic et al. 2010; Teeaar, Liivak et al. 2010). Other groups found small and thereby not relevant sex-related differences only for subgroups (Shaltout, Qabazard et al. 1995). A sex-related difference in incidence was found only in the 10- to 14-year age group with a significantly higher incidence in boys (18.77 vs. 14.7/100,000/year, p = 0.015; Bizzarri, Patera et al. 2010). However, a statistically significantly higher incidence in girls was reported by a Libyan (Kadiki and Roaeid 2002), a Thai (Pana‐ monta, Thamjaroen et al. 2011), and an Australian group (Taplin, Craig et al. 2005). The lat‐

was 3.0% per year (95% CI 2.59-3.33; p < 0.001; Onkamo, Vaananen et al. 1999).

velopment was noticed by estimated data from Colorado (Vehik and Dabelea 2010).

**3.3. Sex-dependent differences of type 1 diabetes mellitus incidence**

The increasing incidence of type 1 diabetes is evident. Although some groups found no age-de‐ pendent differences in the annual increment of type 1 diabetes incidence (Taplin, Craig et al. 2005; Svensson, Lyngaae-Jorgensen et al. 2009; Abduljabbar, Aljubeh et al. 2010), the majority of the published studies reported different increments of incidence after stratifying children and youths into different age groups: Michealis et. al (1993) found an increment of incidence of about 12.6% in 0- to 9-year-old children, in 10- to 19-year-old children the increment was 3.8%. Similar results were reported by other German groups (Neu, Ehehalt et al. 2001; Ehehalt, Blumenstock et al. 2008): the relative increment of type 1 diabetes incidence was 5.7% per year in 0- to 4-year-old children, the other age groups showed smaller increments. The incidence of childhood-onset type 1 diabetes in Estonian children under 15 years of age increased annually by an average of 3.3% with the most rapid annual increase (9.3%) occurring in the youngest age group (Teeaar, Liivak et al. 2010). The EURODIAB register repeatedly confirmed that in Europe the annual in‐ crease of incidence is higher in younger children (0 to 4 years of age; Green and Patterson 2001; Patterson, Dahlquist et al. 2009).

#### **3.5. Seasonal differences of type 1 diabetes mellitus incidence**

When discussing seasonal differences in the epidemiology of type 1 diabetes, two different aspects must be mentioned: 1) different frequency of type 1 diabetes regarding the season of birth, and 2) the changing onset or diagnosis of type 1 diabetes through the year.
