The Incidence of Type 1 Diabetes Is Increasing Faster in Familial Than in Sporadic Cases. Eighteen Years of the Israeli Pediatric Diabetes Registry

Presentation Number: SAT 588
Date of Presentation: April 1st, 2017

Amnon Zung*1, Wasef Na'amnih2 and Orit Blumenfeld2
1Kaplan Medical Center, Rehovot, Israel, 2Israel Centers for Disease Control, Ministry of Health, Tel Hashomer, Israel

Abstract

Objective

The global rise in the incidence of type 1 diabetes (T1D) is too rapid to be attributed to susceptible genetic background, and hence it emphasizes the main role of environmental factors. Unlike the rising theory that the need for genetic susceptibility (mainly HLA class II genes) has lessened over time, we hypothesized that the incidence rise of T1D is faster in genetically susceptible population.

Research design and methods

The study population comprised of 5080 T1D patients aged 0-17 years who were reported to the Israel Diabetes Registry over 18 years (1997-2014). The patients were divided into familial cases where at least another member of the core family has T1D, and sporadic cases. Hospital outpatient records of familial cases were reviewed for unreported familial cases. Data on gender, ethnicity (Jews vs. non-Jews), age at diagnosis, seasonality and ketoacidosis (DKA) at diagnosis were retrieved from the registry. Data on age at diagnosis were divided into four age-groups: 0-4, 5-9, 10-14 and 15-17 years. Annual incidence rates (per 100,000/year) and 95% CIs for the time periods were computed separately for the sporadic and familial cohorts.

Results

The familial cases (n=583; 11.5%) and the sporadic cases (n=4497; 88.5%) were comparable for gender and seasonality, but DKA at diagnosis was twice as common in the sporadic vs. familial cases (40.62% vs. 20.74%; p<0.001), which may reflect high parental awareness to initial symptoms of diabetes. The proportion of non-Jewish cases in the familial group was higher than in the sporadic group: 26.07% vs. 22.73%; p=0.01. This ethnic distribution probably reflects a relatively high prevalence of consanguinity in the non-Jewish population, which leads to the expression of recessive T1D-related genes. The proportion of patients in the youngest age-group (0 to 4 years) tended to be higher in the familial cases: 18.35% vs. 15.45%; p=0.07. Overall, the annual increase in T1D incidence was significantly higher in the familial than the sporadic cases: 4.24% vs. 2.56%; p<0.001.

Conclusions

The fast increase of T1D incidence among familial compared with sporadic cases underscores the key role of genetic susceptibility in the rise of T1D incidence over the last decades. We suggest that the genetically susceptible population is responding vigorously to environmental factors, probably through non-HLA susceptible genes.

 

Nothing to Disclose: AZ, WN, OB