Incidence Of Insulin-dependent Diabetes Mellitus Research Articles

Epidemiology of IDDM in Switzerland. Increasing incidence rate and rural-urban differences in Swiss men born 1948-1972.

To determine the incidence of insulin-dependent diabetes mellitus (IDDM) in Switzerland by undertaking a retrospective analysis of the registry of the Swiss army, which contains updated medical files for all male Swiss citizens. Nation-wide data for IDDM epidemiology have not been available in Switzerland. Every male Swiss citizen is obliged to enlist in the Swiss military service at 19 years of age, when a personal, continuously updated medical file is established. Diabetes is an exclusion condition for military service and is clearly marked in the file. A total number of 514,747 files, corresponding to birth year cohorts 1948-1950, 1955-1957, 1962-1964, and 1970-1972, have been manually checked for the diagnosis of IDDM. IDDM was identified in 926 cases in the four groups of three age-cohorts. The incidence at < or = 15 years (per 100,000/year) was 4.5 in the age cohorts 1948-1950 and 7.2 in the age cohorts 1970-1972 (P < 0.005). An additive age-cohort Poisson regression model fits the nationwide incidences adequately, neither a period effect nor age x cohort interactions being required. In the oldest age cohorts, the age-specific incidence of IDDM was calculated up to the age of 43 and was approximately 7/100,000/year in men between 20 and 40. In these age cohorts, we found an approximately 50% higher risk to develop IDDM at age < or = 19 for men living in an urban region and a significantly (P < 0.005) increased incidence between 20 and 40 years in rural regions compared with urban regions. The incidence of IDDM in Switzerland is comparable to other countries in central Europe and has been increasing in the last 20 years. This is in accordance to most recent epidemiological studies worldwide. In addition, the data suggest exogenous factors inducing IDDM at a younger age in urban regions.

Protection from experimental autoimmune diabetes in the non-obese diabetic mouse with soluble interleukin-1 receptor.

We have evaluated the effects of a treatment with soluble interleukin-1 receptor (sIL-1R) in the accelerated model of autoimmune diabetes induced by cyclophosphamide (CY) in the non-obese diabetic (NOD) mouse. Prior to the CY challenge (350 mgkg body weight), female euglycemic NOD mice were randomly divided into three groups (A-C). Groups B and C were treated daily from 1 day before to 13 days after the CY challenge with sIL-1R at doses of 0.2 and 2 mg/kg body weight. Group A was treated with PBS. By 2 weeks after CY administration, an acute form of autoimmune diabetes with glycosuria, hyperglycemia and severe insulitis occurred in the majority (13/20, 65%) of the control mice (group A). In contrast, repeated injections with sIL-1R protected NOD mice from insulin-dependent diabetes mellitus (IDDM) development in a dose-dependent fashion; the incidence of IDDM was 53.3% (8/15) in the mice treated with 0.2 mg/kg and only 6.7% (1/15) in those treated with 2 mg/kg. However, none of the doses of the sIL-1R reduced the extent of insulitis in NOD mice. Importantly, the anti-diabetogenic property of sIL-1R may not involve major T cell function impairment; accordingly, in parallel experiments, splenic lymphoid cells from NOD mice not challenged with CY, but treated with 2 mg/kg sIL-1R for 5 consecutive days showed a normal distribution of mononuclear cell subsets and maintained their capacity to secrete interferon-gamma and IL-2 and to proliferate in response to polyclonal mitogenic stimulation with concanavalin A.

HLA-DQB1 Codon 57 and IDDM in Chinese Living in Taiwan

To study the human leukocyte antigen (HLA)-DQB1 genetic background in the Chinese population in Taiwan and its association with the low incidence of insulin-dependent diabetes mellitus (IDDM) in this population. Forty-eight IDDM patients and 59 nondiabetic unrelated control subjects were recruited from the population in Taiwan. HLA-DQB1 exon 2 was enzymatically amplified by polymerase chain reaction. HLA-DQB1 alleles were diagnosed by dot blotting and hybridization with 16 sequence-specific oligonucleotide probes. DQB1*0201 and DQB1*0302 alleles were more frequent and DQB1*0301 and DQB1*0601 were less frequent in Chinese with IDDM than in control subjects. Genotypes for homozygous non-aspartic acid residue (NA/NA) at position 57 were positively associated with IDDM at a relative risk of 4.34 (P < 0.001), and those for homozygous aspartic acid (A/A) were negatively associated with IDDM at a relative risk of 0.14 (P < 0.001). Among the NA/A heterozygotes, only DQB1*0201/DQB1*0303 was significantly increased in IDDM subjects. The amino acid residue at position 57 of HLA-DQ beta-chain is significantly associated with the development or prevention of IDDM in Chinese subjects living in Taiwan. Other genetic and environmental factors may also play important roles in pathogenesis of IDDM.

239 ONSET MORTALITY IN INSULIN DEPENDENT DIABETES MELLITUS

From data of the second nationwide incidence study in 1988-1990 on Insulin Dependent Diabetes Mellitus (IDDM) in children aged 0-19 years and of the population based register of mortality data the onset mortality in various age groups was calculated (table). Compared to the previous nationwide study in 1978-1980, the incidence of IDDM had increased, especially in the age group 4-19 years, but the onset mortality risk was significantly lower, although not yet zero. It is important to continue to monitor iht mortality of IDDM cases for trends and to get clues for prevention of such deaths.

Incidence of IDDM in the Marche Region, Italy

To provide reliable data concerning the incidence of insulin-dependent diabetes mellitus (IDDM) in children from the Marche Region in Italy and contribute to a better understanding of its geographical variability throughout Italy and Europe. All newly diagnosed cases of IDDM in children 0-14 years of age in the Marche Region between 1 January 1990 and 31 December 1992 were recorded. The primary source of ascertainment was clinical records from the 59 hospitals of the region. Secondary and tertiary independent sources included local and national associations for diabetic children and local district centers of the National Health System. Over the 3-year study period, the overall IDDM incidence rate was 8.1 per 100,000/year. No significant sex-related difference in incidence was noted, with a male:female ratio of 0.9. The completeness of ascertainment was estimated at 100%. The Marche Region appears to have a slightly elevated incidence of IDDM among noninsular Italian regions.

The pathogenesis of adoptive murine autoimmune diabetes requires an interaction between alpha 4-integrins and vascular cell adhesion molecule-1.

An adoptive transfer model of insulin-dependent diabetes mellitus (IDDM) in the nonobese diabetic mouse was used to examine the roles of alpha 4-integrin, vascular cell adhesion molecule 1 (VCAM-1); and intercellular adhesion molecule 1 (ICAM-1) in the pathogenesis of autoimmune diabetes. Antibodies specific for both alpha 4-integrin and one of its ligands, VCAM-1, were able to delay onset of diabetes and decrease the incidence of the disease in adoptive transfer studies. This blocking of disease was accompanied by a marked decrease in lymphocytic infiltration of the islets of Langerhans. Furthermore, these antibodies preferentially block entrance of CD4 T cells into the tissue. Antibodies specific for ICAM-1 had little effect on the onset or incidence of IDDM. Thus, we conclude that an alpha 4-integrin-VCAM-1 interaction is important in T cell entry into the islets of Langerhans and in the pathogenesis of IDDM. In addition, the cascade of events leading to T cell transit across endothelium may be different for CD4 and CD8 cells, and may differ depending on the endothelium involved. Our results support the more general conclusion that an alpha 4-integrin-VCAM-1 interaction may be crucial in allowing activated effector CD4T cells to leave the blood and enter tissue to clear infection.

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.

Incidence of insulin-dependent diabetes mellitus in young adults: experience of 1,587,630 US Navy enlisted personnel.

First hospitalizations (n = 1,293) for diabetes mellitus between 1974 and 1988 were used as a surrogate for insulin-dependent diabetes mellitus incidence among 17-34-year-old US Navy enlisted personnel followed for 6,077,856 person-years. In the 15-year period, the overall incidence of insulin-dependent diabetes mellitus was 21.3 per 100,000 person-years. Incidence did not differ significantly by sex, but was higher for blacks than whites (28.4 vs. 20.2 per 100,000 person-years, respectively; p < 0.05). Incidence increased with age threefold for white men and fivefold for black men (p < 0.05) between the ages of 17-19 and 30-34 years.

Epidemic outbreaks of insulin-dependent diabetes mellitus

Analysis of annual and seasonal incidence of insulin-dependent diabetes mellitus in children living in 4 Russian cities in the 1980s has shown only four rises of annual morbidity in three cities, but only one of them recorded in 1983 in Moscow conformed to the criteria of an epidemic outbreak of the disease. The incidence of the disease predominated by 29% in autumn-winter, though there was no clear-cut correlation between diabetes incidence, on the one hand, and incidence of influenza and acute respiratory diseases, on the other.

Prevention of insulin-dependent diabetes mellitus by 2′-deoxycoformycin in the BB Wistar rat

The effect of the adenosine deaminase (ADA) inhibitor 2′-deoxycoformycin (dCF) on the development of insulin-dependent diabetes mellitus (IDDM) was assessed in the BB Wistar rat. Sixty-one male rats were treated from days 30 to 120 with 0, 0.5, 1.0 or 1.5 mg dCF/kg/week. The incidence of IDDM was 78% in the controls and was significantly ( P < 0.01) decreased in rats receiving 1.5 mg dCF/kg/week (32%), but not in rats receiving lower doses of the drug. However, for those rats that became diabetic the mean time to the development of IDDM was unchanged in animals receiving dCF compared with control. dCF treatment did not produce significant weight loss in the animals or gross changes in the thymus, spleen or kidneys. Although the protective effect of dCF against IDDM was likely produced by immunosuppression, the different dCF dosages had similar effects on ADA suppression in spleen or thymus and on dATP accumulation in these organs.

Estimation of the prevalence of diabetes mellitus diagnosed, and incidence of type 1 (insulin-dependent) diabetes mellitus in the Avila Health Care region of Spain

We studied the prevalence of diabetes mellitus diagnosed in the Avila Health Care region, Spain, based on the prescribed daily dosage (PDD) of insulin (corrected in function of insulin loss (PDDc)) and sulphonureas, from a sample representative of prescribing physicians (A, n = 48) and pharmacies (B, n = 25) in our region. The amounts of the PDDcs of insulin sold during 1989 per 1000 inhabitants/day were 6.06 and 6.20, respectively for the two samples (A and B). The figures for PDDs of sulphonurea/1000 inhabitants/day were 16.25 and 19.16, respectively. We determined the proportion that diabetic patients on diet alone represented in relation to non-insulin treated diabetic patients who visited the only specialized clinic for diabetic patients in our province in 1989. These patients accounted for 40.83% of non-insulin treated diabetic patients. The patients being treated with biguanides or with a combination of anti-diabetic drugs accounted for less than 1% of those treated in the specialized clinic. Taking this into account, the prevalence of diabetes mellitus in Avila was 3.35% (C.I. 95%: 3.10–3.59), according to the sample A and 3.85% (C.I. 95%: 3.50–4.31) according to the sample B. In addition, we studied the hospital admission records during three consecutive years in order to find out the incidence of type 1 insulin-dependent diabetes mellitus (IDDM) below 15 years of age in the Avila Health Care region of Spain. All prescribing physicians that did not work in the Hospital (197 in the rural area and 18 in the urban area) were used as the secondary source for validation of case ascertainment. The incidence of IDDM per 100 000 inhabitants/year, adjusted to the World Standard Population, was 14.93 (C.I. 95%: 8.6–23.7), male 15.31 (C.I. 95%: 7.0–27.6) and female 14.35 (C.I. 95%: 6.1–28.1). The ascertainment was 100%. The data show that the incidence of IDDM is higher than those reported by other Mediterranean countries, being inconsistent with the hypothesis of a north-south gradient in diabetes risk and that the prevalence is also higher than previously reported. Further studies are needed to determine these data in other regions of Spain.

The ethnic distribution of antibodies to glutamic acid decarboxylase: Presence and levels in insulin-dependent diabetes mellitus in Europid and Asian subjects

Our objective was to ascertain the frequency of antibodies to glutamic acid decarboxylase (GAD) in Europids and four Asian ethnic groups with insulin-dependent diabetes mellitus (IDDM) to gain insight into why the prevalence and incidence of IDDM varies so widely among ethnic and/or geographically diverse population groups. The subjects in this study were Europid ( n = 49), Japanese ( n = 16), Thai ( n = 7), Korean ( n = 21), and Chinese ( n = 13) persons with IDDM with a duration ranging from 5 to 14 years. There were similar numbers of healthy controls matched for each ethnic group. A validated radioimmunoprecipitation assay used GAD from pig brain radiolabeled with 125I using chloramine T. Islet cell cytoplasmic antibodies measured by indirect immunofluorescence were expressed as Juvenile Diabetes Foundation units. The prevalence of antibodies to GAD, compared with Europids (63%), was much lower in all Asian populations with IDDM: Japanese (31%), Thai (29%), Korean (5%), and Chinese (27%). The mean level of antibodies to GAD, however, among diabetics from each population who gave a positive reaction, was similar. For all groups, the prevalence of antibodies to GAD was much higher than that of islet cell cytoplasmic antibodies. Almost all IDDM subjects positive for islet cell antibodies had antibodies to GAD, but the converse did not hold. A radioimmunoprecipitation assay for antibodies to GAD applied to serum from subjects with IDDM in various ethnic groups showed that Europids with IDDM had a much higher prevalence of such antibodies than did Asians. This held for all ethnic groups, and particularly Koreans. Thus, among different populations, there may be etiologic heterogeneity of IDDM. Alternatively, if an autoimmune process is generally operative, different pancreatic autoantigens are involved.

Epidemiology of childhood diabetes in Osaka District, Japan, using the documents from the medical benefits system specific for childhood diabetes

For an epidemiological study of childhood diabetes, application forms for medical benefits filed in Osaka Prefecture were collected and analyzed. A total of 465 patients with childhood diabetes under 18 yr of age were identified during the period between 1978 and 1988; 371 (175 boys and 196 girls) of them were classified as insulin-dependent diabetes mellitus (IDDM), and the others were either non-insulin-dependent diabetes mellitus (NIDDM) or an unidentified type of diabetes. The mean annual incidence of IDDM was 1.68 for boys and 2.00 for girls per 100 000 population, the rate being slightly higher for girls. The rates increased among older children, with a peak in the 10–14-yr age group. The prevalence estimated on the basis of the cumulative incidence in 1988 was 1.29 for boys and 1.60 for girls per 10 000 population, indicating a marked increasing trend with age. A significant seasonal variation was observed in the months of onset for IDDM, with higher rates during the winter. The mean birth weights of the male and female patients with IDDM were slightly lower than the national means. Use of official documents obtained from the medical benefits system was found to be an effective method for identification of cases of IDDM in the community, although further information is required for more accurate confirmation of such cases.

Low Incidence of Childhood IDDM in District of Novosibirsk (Russia)

To study the incidence of insulin-dependent diabetes mellitus (IDDM) among 0- to 14-yr-old children of the district of Novosibirsk, in western Siberia, Russia, from 1983 to 1989. Data were collected with methods recommended by the Diabetes Epidemiology Research International Group. The average yearly incidence among males and females was 4.7 (95% confidence interval 3.9-5.8) and 4.4 (95% confidence interval 3.6-5.4) per 100,000 people, respectively. The incidence of IDDM among children living in the city of Novosibirsk was significantly higher than in children living in the surrounding counties of the district, 5.7/100,000 (95% confidence interval 4.8-6.8) versus 3.6/100,000 (95% confidence interval 2.9-4.5). The incidence of childhood IDDM among Russians in Siberia is low. This is the first publication of internationally comparable data on the occurrence of childhood IDDM in the Russian population.

Temporal variation in incidence of IDDM in Canterbury, New Zealand.

To establish the statistical significance of observed variations over the last decade in the incidence of insulin-dependent diabetes mellitus (IDDM) in the 0- to 19-yr-old age-group and to determine whether incidence has increased in Canterbury, New Zealand. The Canterbury, New Zealand, Diabetes Registry has recorded all incidence cases of diabetes mellitus prospectively since 1982. All IDDM subjects aged 0-19 yr at diagnosis and using insulin are included in the study. Ascertainment is believed to be 100%. Prevalence was recorded at 1 January 1982 and 1 January 1990. Annual incidence for 1982-1990 was determined using age and sex cross-sectional census population denominators. The statistical significance of temporal, age, sex, and seasonal variations in incidence rates was ascertained by Poisson regression models (GLIM statistical software). Prevalence on 1 January 1990 was 115/100,000. Incidence rates during the 9 yr were periodic, with two major peaks--one in the early 1980s, the other in 1989 continuing into 1990. The temporal variation (P less than 0.02) was not age or sex specific. Incidence rates for boys were three- to fourfold higher during peak versus trough years, with a peak level of 20.7/100,000 in 1990. For girls, there was less variation, with a peak rate of 21.6/100,000 in 1990. There has been no significant increase in IDDM incidence over time. The mean rate of incidence across all age-groups for 1982-1990 was 12.7/100,000 person-yr. A significant seasonal association to the onset of IDDM was found only in boys, with incidence rates being significantly higher in winter than in summer (P less than 0.01). IDDM in Canterbury, New Zealand, presents in cycles of incidence peaks and troughs, each spanning 2-3 yr.

Diabetic Ketoacidosis: Pathophysiology, Management and Complications

Diabetic ketoacidosis (DKA) is a common and potentially life-threatening complication of diabetes mellitus, the second most common chronic childhood disease [1]. Prior to the introduction of insulin to clinical medicine by Banting and Best in 1922, DKA had a mortality rate greater than 60% [2]. As insulin was introduced into clinical practice, there was a gradual decrease in mortality associated with DKA over the subsequent 30 years. Recent epidemiological data reveal current mortality varies from 0 to 19% [3,4]. DKA continues to be the most common cause of death in patients younger than 24 years of age; it accounts for as many as 50% of deaths of young diabetic patients [5–7]. In elderly diabetics who have coexisting diseases, DKA carries a high mortality [8]. Despite many advances in the care of diabetic patients, the prevalence of DKA is not declining; it accounts for 14% of all diabetes-related hospital admissions [3, 4, 9]. The incidence of insulin-dependent diabetes mellitus continues to increase worldwide and has roughly doubled in each recent decade [10–13]. Because insulin-dependent diabetes mellitus is increasing, and preventative measures to avoid DKA in diabetic patients have not been successful, the incidence of DKA can also be expected to increase in coming years. Prevention of DKA is the ultimate goal (80% of hospital admissions for DKA occur in treated diabetics) [3,8]. It is necessary for clinicians to understand the pathophysiology and treatment of DKA to care for this increasing diabetic population. We discuss the pathophysiology of diabetic ketoacidosis, its management, and its complications.

The HLA DQB1*0502 allele is neutrally associated with insulin-dependent diabetes mellitus in the Sardinian population.

In the Sardinian population a very high incidence of insulin-dependent diabetes mellitus (IDDM) and the lack of HLA-DR2 protective effect due to the high frequency of the A2, Cw7, B17, 3F31, DR2, DQw1 extended haplotype has been reported. This haplotype, carrying a Serine at position 57 of the DQB1*0502 allele, has been previously reported to be underrepresented in patients when compared to controls. In order to provide an explanation for this finding, we defined by RFLP analysis the HLA haplotype of 45 Sardinian IDDM patients and 49 controls. All DR-2DQw1 subjects were molecularly characterized at the HLA DQA and DQB loci. All DR2-positive patients and the vast majority of the DR2-positive controls had the DQB1*0502 allele at the DR2-linked DQB1 locus, with no statistically significant difference between the two groups. All DQA1 genes were the ones expected, with only two exceptions. Nine out of 10 of the DR2-positive patients were compound heterozygotes for DQB1*0201/DQB1*0502 alleles; only this allele combination was significantly increased (p less than 0.0003). Our data suggests that a) the DQB1*0502 allele is neutral for IDDM development and b) the susceptibility to IDDM in our DR2-positive patients is related to the compound heterozygous state between the neutral DQA1*0102/DQB1*0502 and the susceptibility DQA1*0501/DQB1*0201 alleles.

Incidence of IDDM in Western Australia in children aged 0-14 yr from 1985 to 1989.

To document the incidence of insulin-dependent diabetes mellitus (IDDM) in Western Australia in children aged 0-14 yr between 1985 and 1989 and to test for differences in incidence by year of diagnosis, age of diagnosis, and sex. A population-based register that used a primary source of case ascertainment (diabetes clinics at teaching hospitals and direct approach to general practitioners and general physicians) and a secondary source (Western Australian Hospital Morbidity Data System) established numerator data. Denominator data were obtained from the Australian Bureau of Statistics. From 1985 to 1989 inclusive, 235 children in the 0- to 14-yr age-group were diagnosed with IDDM in Western Australia. Case ascertainment was estimated at 99% complete. The mean age-adjusted (developed-world population) annual incidence of IDDM was 13.2 per 100,000 person-yr and there was no evidence of an increasing incidence over the 5 yr. However, girls were more likely than boys to be diagnosed with IDDM in this period (P = 0.006). The incidence of IDDM in Western Australia is in the middle range of IDDM incidence in countries throughout the world. The unexpected finding of an increased incidence of IDDM in girls compared with boys needs to be confirmed in a future study.

EPIDEMIOLOGICAL STUDY OF INSULIN-DEPENDENT DIABETES MELLITUS IN CHILDREN IN GUNMA

The prevalence and incidence of insulin-dependent diabetes mellitus (IDDM) in children under 18 years of age in Gunma were studied using information obtained from questionnaires sent to hospitals in Gunma prefecture.The number of IDDM patients was 80 (31 boys and 49 girls) in March of 1991. The prevalence and incidence of IDDM were 1.65/10, 000 and 1.71/100, 000, respectively. The incidence was very similar to those found in other areas of Japan. However, the prevalence was slightly higher. Thirty percent of IDDM patients were identified at school physical check-ups, because of glucosuria and 58.3% of these patients had already shown diabetic symptoms such as polyuria and polydypsia.

Genetic Epidemiology of Insulin-Dependent Diabetes Mellitus: International Comparisons Using Molecular Genetics

International comparative molecular studies of insulin-dependent diabetes mellitus can be viewed from an immunogenetical and an epidemiological perspective. Each approach independently contributes to our knowledge concerning the etiology and prevention of the disease. However, the combination of these perspectives, representing an interface between molecular biology and epidemiology, will achieve more in terms of scientific advancement and public health than either perspective alone. An excellent example of the development of molecular epidemiology has been the evolution of international comparative research through the WHO Multinational Project for Childhood Diabetes. Case-control molecular studies are currently being conducted to test the hypothesis that population variation in the frequency of HLA class II susceptibility alleles is the primary determinant of the global patterns of insulin-dependent diabetes mellitus incidence. Preliminary data suggest that this hypothesis is correct. Future international molecular epidemiological studies, encompassing host-environment interactions, will lead to a better understanding of the relationships among specific risk factors within populations and across the world. Molecular epidemiology represents a new paradigm for studying the etiology and epidemiology of infectious and non-communicable diseases, and no doubt represents a major challenge for the 1990s.