High Incidence Of Insulin-dependent Diabetes Mellitus Research Articles

Diabetes and enterovirus autoimmunity in glacial Europe

The incidence of insulin-dependent diabetes mellitus (IDDM), a chronic disease with a well-known genetic basis, is highest in Scandinavian and Sardinian populations. The high incidence of IDDM in Scandinavia and Sardinia, which were genetically isolated from the spread of agriculturists in Europe about 8000 years ago, suggests that an IDDM-susceptible genotype(s) may have been beneficial in Europe more than 8000 years ago. In glacial times, Europe had an extremely cold climate that was frequently interrupted by episodes of warming. When enteroviruses were locked in the ice and permafrost, glacial Europeans would have had little immunity to these viruses. Each time the climate warmed, enteroviruses would have spread through increased amounts of melt water. With a genetic ability to mount an autoimmune defense, the IDDM genotype(s) would have been beneficial in glacial Europe as a defense against all enteroviruses, including those that had co-evolved to mimic host tissue.

Lack of seasonality in the month of onset of childhood IDDM (0.7-15 years) in Shanghai, China.

A cohort of 136 children from Shanghai with insulin dependent diabetes mellitus (IDDM) (0.7-15 years) were analyzed for the month of onset of disease and month of birth. In contradistinction to populations with a medium or high incidence of IDDM, no seasonality was registered in the month of onset. On the other hand there was a significant (p < 0.026) seasonality in the month of birth (peak November to January), but which differed in pattern to that observed in populations with medium or high incidence. Our findings support the hypothesis that the initiation of IDDM is due to a viral infection and that one cause for the low incidence of childhood IDDM in certain populations is immunization against infectious pathogens in their early life.

Insulin-dependent diabetes mellitus in Sardinian-heritage children living in Lombardy

The contributions of genetic and environmental factors to insulin-dependent diabetes mellitus (IDDM) susceptibility are uncertain. Children born and living in Lazio, which has a low incidence of IDDM, have the same high incidence of IDDM as their Sardinian parents.1 We studied Sardinian-heritage children in Lombardy, an Italian region with the same low incidence of IDDM as Lazio.

Islet cell surface antibodies are more common in patients and relatives in areas and during seasons with high incidence of insulin-dependent diabetes mellitus.

Although existence of islet cell antibodies (ICA) is regarded as secondary to beta cell death, islet cell surface antibodies (ICSA) might play a role in the disease process. We have collected information from nine European clinics to determine whether ICSA are more common in diabetic children or their relatives in geographical areas or time periods of high incidence of insulin-dependent diabetes mellitus (IDDM). In Finland and Sweden ("North group") with a high incidence of IDDM during childhood, 36% of the patients were positive or weakly positive for ICSA at diagnosis compared with 24% in France (p = 0.1), 11% in Berlin-Vienna (p < 0.01), and 14% in Italy (p < 0.01). This difference was seen in all age groups but was most pronounced in the youngest (0-4 y). This geographical difference was also seen among family members of whom 46% were positive or weakly positive in the North group, 25% in France (p < 0.001), 21% in Berlin-Vienna (p < 0.001), and 16% in Italy (p < 0.001). Of several analyzed antibodies (ICA, gastric parietal cell, thyroglobulin, and thyroid microsomal), only ICSA showed simultaneous positivity in all family members (r = 0.32, p < 0.01). ICSA were most common in family members of patients with short (< 8 d) duration of symptoms (p < 0.05) and showed a similar seasonality, both in patients and relatives, as the incidence of IDDM. We conclude that the geographical difference in incidence of childhood IDDM in Europe may be associated to similar geographical differences in occurrence of ICSA both in newly diagnosed diabetic children and in their relatives. Simultaneous existence of ICSA in both patients and family members and a similar seasonality for ICSA and incidence of IDDM suggest that ICSA may reflect an ongoing disease process.

High Incidence of Childhood-Onset IDDM in Kuwait

To determine the incidence of insulin-dependent diabetes mellitus (IDDM) in children aged 0-14 years in Kuwait, as part of the World Health Organization Multinational Collaborative Study (DIAMOND), and to determine if the incidence rates have increased. All cases of IDDM diagnosed before the child's 15th birthday between 1 January 1992 and 31 December 1993 were recorded. Prospective notification of all children with newly diagnosed diabetes who were admitted to hospitals and periodic review of hospital medical records provided the primary source; notification by physicians working in diabetic clinics, in which registry of all new cases is mandatory, provided the secondary source of ascertainment. The degree of ascertainment was 92.2%. The annual incidence of IDDM for children aged 0-14 years over the 2-year period was 15.4/100,000 (95% confidence interval, 12.4-19), with a male:female ratio of 1.2:1. The age-specific annual incidence rates for the age-groups 0-4, 5-9, and 10-14 years were 12.8, 15.1, and 18.3/100,000, respectively, with a male:female ratio of 1.45:1 in the 0- to 4-year-old age-group and an equal sex ratio in the 5- to 9- and 10- to 14-year-old age-groups. No significant difference was detected between incidence rates of IDDM in boys and girls in the three age-groups. There was no significant linear trend toward an increase in IDDM incidence rates as age advanced. Compared with a previous study by Taha et al. (Taha T, Moussa M, Rashed A, Fenech F: Diabetes mellitus in Kuwait: incidence in the first 29 years of life. Diabetologia 25:306-308, 1983), there was a nearly fourfold increase of IDDM in the age-group 0-14 years, mainly in those children < 5 years old, suggesting a rapid increase in a short period of time. Kuwait has the highest incidence of IDDM in children in the region, and an apparently increasing incidence has been demonstrated over the last decade.

Relationship between dairy product consumption and incidence of IDDM in childhood in Italy.

To test the hypothesis that the consumption of dairy products, including fluid cows' milk and cheese, is related to the incidence of insulin-dependent diabetes mellitus (IDDM), we correlated incidence rates in children 0-14 years of age with cows' milk and cheese consumption in nine regions of a single country, Italy. Data on the incidence of IDDM were derived from the only nine Italian regions where primary and secondary sources of ascertainment were available for 1991. Data on fluid cows' milk and cheese consumption in the corresponding year in each region were obtained from the National Institute of Statistics. The correlation between fluid milk consumption and incidence of IDDM in Italy was 0.84 (P < 0.004, Poisson regression analysis). Cheese consumption was not related to IDDM incidence. The results indicate that there is a relationship, even in a single country, between dairy product consumption and the incidence of IDDM that is confined to fluid milk consumption. Cows' milk may contain a triggering factor for the development of diabetes, but the high incidence of IDDM in Sardinia and in other countries worldwide cannot be explained simply by the quantity of fluid cows' milk consumed.

Space-time clustering in insulin-dependent diabetes mellitus (IDDM) in south-east Sweden.

Using the method developed by Knox, space-time clustering was analysed in all 584 cases of insulin-dependent diabetes mellitus (IDDM) diagnosed between 1977-1990 and below the age of 16 from four paediatric departments in south-east Sweden. The catchment areas of these clinics form a contiguous geographical area of 26,445 km2 with a total of 165,784 children aged 0-15 years. The annual incidence for the study period was 25.2 per 100,000 children aged 0-15 years with a statistically significant incidence variation between the years; highest incidence in 1983 (39.2) and lowest in 1977 and 1989 (18.9 and 20.7 respectively). In the analysis, 30 different combinations of critical cutoff values were used to define closeness in space and time of pairs of cases. Statistically significant results were seen for several combinations with the highest significance obtained for the cutoff values of 15 km and 7 months, respectively. This space-time clustering tended to be specially pronounced during the period with the highest incidence of IDDM, 1981-1985. Our results indicate that space-time clustering exists in IDDM. These findings may support the hypothesis that infectious agents (possibly viral) give rise to a portion of IDDM.

HLA-DQB1 Alleles and Absence of Asp 57 as Susceptibility Factors of IDDM in Finland

It has been proposed that negatively charged aspartic acid at position 57 of the HLA-DQ beta-chain determines resistance to development of insulin-dependent diabetes mellitus (IDDM), whereas genetic susceptibility to IDDM correlates with a neutral amino acid residue. The disease rate is very low in Oriental populations with high frequencies of Asp 57. This raises a question whether the high incidence of IDDM in Finland could be explained by the distribution of this disease marker. In this study, the polymerase chain reaction products of 86 diabetic patients and 115 nondiabetic control subjects were analyzed with seven sequence-specific oligonucleotide probes. Only 25.5% of the diabetic subjects were phenotyped as Asp 57+ compared to 82% of control subjects, which suggests that Asp 57 negativity is a definite risk marker for developing IDDM in Finnish patients. However, the susceptibility conferred by various non-Asp and Asp haplotypes was not equally strong: DQw8 was the most important risk marker and DQw6 the most protective one. The frequency of Asp 57+ DQw4 was similar in diabetic patients and control subjects. The highest genotype-associated relative risk was defined by DQw2/DQw8 heterozygosity (RR 91), whereas it was 13 for non-Asp homozygosity. In the control subjects, the frequency of Asp 57+ phenotypes was higher than in several white populations with lower IDDM incidence figures. We conclude that the disease risk in Finland appears to be most strongly related to specific Asp 57- alleles, although other HLA- or non-HLA-associated genes may also contribute to IDDM susceptibility in this population.

Comparison of Incidence of IDDM in Childhood Between Estonia and Finland, 1980–1988

To compare nationwide incidence of childhood insulin-dependent diabetes mellitus (IDDM) in children aged 0-14 yr between Estonia and Finland during 1980-1988. For Estonia, which has a population genetically and linguistically related to Finland, only limited information was available. Finland has the highest incidence of IDDM in the world. The registration of all new cases of IDDM in Estonia was conducted by the local district pediatricians who reported every newly diagnosed diabetic patient to the Republic Endocrinology Centre. Registration of all new cases of IDDM in Finland was based on the statistics of the Social Insurance Institution, which approves free-of-charge insulin treatment for diabetes. These data were validated with one or more additional data sources. The case ascertainment rate approached 100% in both countries. The average yearly incidence of IDDM standardized for age for the years 1980-1988 in Estonia was approximately 33% of that in Finland. Among males it was 11.3 (95% confidence interval [CI] 10.3-12.3) per 100,000 in Estonia and 35.1 (95% CI 33.4-36.9) per 100,000 in Finland, and among females 10.1 (95% CI 9.2-11.1) per 100,000 in Estonia and 30.4 (95% CI 28.8-32.1) per 100,000 in Finland. When the two periods 1980-1982 and 1986-1988 were compared, the age-standardized incidence in Estonia remained unchanged, whereas in Finland it increased approximately 20%. The data between two populations who are ethnically and linguistically similar and live geographically close but in a different environment, provides further evidence that both genetic and environmental factors are contributing to the risk of IDDM.