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G Joner

Publications and source records attributed to G Joner.

33 records · Page 2Linked to original sources

HLA-encoded genetic predisposition in IDDM: DR4 subtypes may be associated with different degrees of protection.

Recent studies have shown that the risk conferred by the high-risk DQA1*03-DQB1*0302 (DQ8) haplotype is modified by the DRB1*04 allele that is also carried by this haplotype. However, many of these studies suffer from lack of sufficient numbers of DQ-matched control subjects, which are necessary because there is a strong linkage disequilibrium between genes in the HLA complex. In the present study, using a large material of IDDM patients and DQ-matched control subjects, we have addressed the contribution of DR4 subtypes to IDDM susceptibility. Our data, together with recent data from others, clearly demonstrate that some DR4-DQ8 haplotypes are associated with disease susceptibility, while others are associated with protection, depending on the DRB1*04 allele carried by the same haplotype. In particular, our data demonstrate that DRB1*0401 confers a higher risk than DRB1*0404. Based on combined available data on the genetic susceptibility encoded by various DR4-DQ8 haplotypes and the amino acid composition of the involved DRbeta*04 chains as well as the ligand motifs for these DR4 subtypes, we have developed a unifying hypothesis explaining the different risks associated with different DR4-DQ8 haplotypes. We suggest that disease susceptibility is mainly conferred by DQ8 while DR4 subtypes confer different degrees of protection. Some DR4 subtypes (i.e., DRB1*0405, 0402, and 0401) confer little or no protection, while others (i.e., DRB1*0404, 0403, and 0406) cause an increasing degree of protection, possibly by binding a common protective peptide. Features of a protective peptide that fit such a model are briefly discussed.

Adolescent↗

No independent associations of LMP2 and LMP7 polymorphisms with susceptibility to develop IDDM.

Results from a recent study suggested that polymorphisms within the HLA class II genes LMP2 and LMP7 were associated with the susceptibility for developing IDDM, and that this association could not be explained by linkage disequilibrium to HLA-DR or -DQ genes. We typed 285 IDDM patients and 337 HLA-DRB1-DQA1-DQB1 genotypically matched control subjects from an ethnically homogeneous population for both the G/T polymorphism in intron 6 of the LMP7 gene and the Arg-His polymorphism in the LMP2 gene. In addition, we typed IDDM families in which at least one parent was homozygous for a DRB1-DQA1-DQB1 haplotype and performed a transmission/disequilibrium test of these LMP polymorphisms. Our data suggest that none of these LMP2 or LMP7 polymorphisms are independently associated with IDDM susceptibility, in contrast to what has been previously reported by others. Further, our results suggest that one partial explanation for the previously reported independent association between IDDM and these LMP polymorphisms may have been that patients and control subjects were not matched for DRB1*04 subtypes. Our results emphasize the need for a complete matching for DRB1, DQA1, and DQB1 alleles between patients and control subjects when attempting to detect independent effects of other polymorphisms in the HLA complex on IDDM susceptibility or protection.

Cysteine Endopeptidases↗

A nationwide cross-sectional study of retinopathy and microalbuminuria in young Norwegian type 1 (insulin-dependent) diabetic patients.

A nationwide cohort of Type 1 (insulin-dependent) diabetic patients was studied to determine the prevalence of retinopathy and microalbuminuria and to evaluate the association to various risk factors. Of 600 subjects with mean age of 19.8 years (range 8.0-30.3) and a mean duration of diabetes of 10.5 years (range 6.2-17.3), 371 (60%) volunteered for a clinical examination which included fundus photography, timed overnight urine samples for albumin excretion rate, measurement of arterial blood pressure and determination of HbA1c. Retinopathy was found in 122 of 371 patients (32.8%), in 3 of 41 (7.3%) patients aged less than 13 years. The youngest subject with retinopathy was 9.6 years old. Microalbuminuria was found in 44 of 351 patients (12.5%), in 1 of 41 (2.4%) patients aged less than 13 years. The youngest subject with microalbuminuria was 11.5 years old. Mean HbA1c was 8.6% (normal range 4.5-601%). Patients with retinopathy had significantly higher mean age (p = 0.0001), longer mean duration of diabetes (p = 0.0001), higher mean HbA1c (p = 0.009), and higher mean arterial blood pressure (p = 0.0001) compared to patients without retinopathy. In microalbuminuric patients HbA1c (p = 0.001) and mean arterial blood pressure (p = 0.01) were significantly higher compared to non-microalbuminuric patients, but there was no difference in age or diabetes duration. In a multiple logistic regression model, age, HbA1c, duration of diabetes and mean arterial blood pressure were found to be significantly associated with retinopathy, while HbA1c, mean arterial blood pressure and onset before 13.0 years of age were found to be associated with microalbuminuria.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

The mortality of children with type 1 (insulin-dependent) diabetes mellitus in Norway, 1973-1988.

The mortality status of all individuals in Norway with the onset of Type 1 (insulin-dependent) diabetes mellitus from 1973 through 1982 and age at onset below 15 years was determined as of 1 July 1988. Of the 1908 cases included in the follow-up, 20 had died (15 males and 5 females) and 10 had emigrated. A two-fold increased risk for early mortality was exhibited among this cohort. Life-table analyses did not find sex or age at onset of Type 1 diabetes to be statistically significant predictors of survival when controlling for diabetes duration. A review of death certificates revealed that accidents and suicides accounted for 40% of the deaths in the total cohort and that this cause of death occurred only among male subjects. Acute diabetes related complications were the underlying causes of death for 35% of the subjects. Diabetic renal disease and death by cardiovascular disease were not documented in this young cohort with a maximum age of 30 years and maximum diabetes duration of 15.5 years. This is the first mortality report of a population-based registered cohort of Type 1 diabetic patients for Norway. While still being at increased risk for premature death, this cohort appears to be at decreased risk of early death when compared to a cohort of young diabetic patients from Oslo, Norway diagnosed in 1925-1955, suggesting improvements in the survival of individuals with Type 1 diabetes in Norway.

Adolescent↗

The incidence of type 1 (insulin-dependent) diabetes mellitus 15-29 years in Norway 1978-1982.

All new cases of Type 1 (insulin-dependent) diabetes mellitus in the 15-29 year age group during the five-year period 1978-1982 were registered using a retrospective technique on a nation-wide basis. A total of 784 newly diagnosed cases were detected, from an average population of 926,192. The degree of ascertainment was almost 90%. The mean yearly incidence for the five-year period was 17.0 per 100,000. The observed incidence is doubled compared to the incidence found in the city of Oslo during the years 1956-1964 (8.8 per 100,000). The male incidence exceeded the female incidence by 12% (p less than 0.05). There was a marked geographic variation in incidence, with a higher incidence in the three southern health regions compared to the two northern, 18.3 vs 13.9 per 100,000 (p less than 0.01). There was a significant seasonal trend in the incidence data (p less than 0.025) with the highest number of new cases detected in the months of January and September and the lowest number in July. In conclusion, the study suggests a two-fold increase of incidence of diabetes mellitus in the age group 15-29 years during the last 2-3 decades and a geographic variation in incidence within the country, pointing to the operation of environmental pathogenic factors.

Adolescent↗

Relationship between cows' milk consumption and incidence of IDDM in childhood.

OBJECTIVE: To compare age-standardized incidence rates of diabetes in children 0-14 yr of age and cows' milk consumption in various countries. RESEARCH DESIGN AND METHODS: Ecological correlation study. Only incidence rates from diabetes registries carefully validated by the Diabetes Epidemiology Research International Study Group were used-Finland, Sweden, Norway, Great Britain, Denmark, United States, New Zealand, Netherlands, Canada, France, Israel, and Japan. Data on fluid cows' milk consumption in corresponding countries were obtained from the International Dairy Federation. RESULTS: Correlation between milk consumption and incidence of insulin-dependent diabetes mellitus (IDDM) was 0.96. The data fit a linear regression model, and analysis showed that 94% of the geographic variation in incidence might be explained by differences in milk consumption. CONCLUSIONS: The results support the hypothesis that cows' milk may contain a triggering factor for the development of IDDM.

Adolescent↗

Increasing incidence of diabetes mellitus in Norwegian children 0-14 years of age 1973-1982.

A retrospective technique was used to register all newly diagnosed cases of diabetes mellitus in Norwegian children 0-14 years of age during the ten-year period 1973-1982. A total of 1,914 newly diagnosed cases were detected, from an average population of 932,037 children. The degree of ascertainment was near to 99%. The male incidence exceeded the female incidence by 12% (p less than 0.02). The mean yearly incidence for the ten-year period was 20.5 per 100,000. Comparing the two five-year periods 1973-1977 and 1978-1982, the mean yearly incidence increased from 18.5 to 22.7 per 100,000 (p less than 0.0001). There was a marked geographic variation with the highest incidence in the south-east and lower incidence in the northern part of the country. However, in the northern part of the country, there was a remarkable increase of the annual incidence from the first to the second five-year period (12.9 vs 19.3 per 100,000). The highest numbers of new cases were detected in the months of January and October, and the lowest numbers in May and July. The seasonal pattern was significantly different from a uniform distribution of new cases throughout the year (p less than 0.001). The age-specific incidence increased towards a peak at 12 years for both sexes. In conclusion, Norway has a high and apparently increasing incidence of childhood diabetes. The geographic variation and secular trend present challenging clues for a search of etio-pathogenic factors.

Adolescent↗

Relation between breast-feeding and incidence rates of insulin-dependent diabetes mellitus. A hypothesis.

The variations in incidence rates of insulin-dependent diabetes mellitus (IDDM) in childhood within and between genetically very similar Scandinavian populations and the variations in incidence rates with time are difficult to explain. Epidemiological data show that the incidence of childhood IDDM may now be declining and suggest an inverse correlation between breast-feeding frequency and IDDM in childhood. Case-control data show that diabetic children were breast-fed for shorter periods of time than their healthy siblings and the population at large and that a smaller proportion of diabetic children were ever breast-fed. It is postulated that insufficient breast-feeding of genetically susceptible newborn infants may lead to beta-cell infection and IDDM later in life.

Adolescent↗

Incidence, age at onset and seasonal variation of diabetes mellitus in Norwegian children, 1973-1977.

A retrospective study was undertaken to estimate the incidence of diabetes mellitus in Norwegian children. Data were collected from all hospitals in the country and from a central insurance register. Eight hundred and forty-five new cases in the age group 0-14 years and with onset in the five-year study period 1973-1977 were detected. The calculated mean annual incidence was 17.6 per 100 000 children, with a year-to-year variation of 15.4-19.3 per 100 000. The geographic variation in incidence was considerable with the lowest rate in the North (6.8/100 000/year) and the highest rates in the South-Eastern part of the country (approx. 20/100 000/year). There was a significantly higher incidence for boys (18.8/100 000/year) than for girls (16.4/100 000/year). The age variation in the incidence rates showed rising values towards a peak at 12 years for girls and a plateau at 12-14 years for boys, with an abrupt decline after 12 and 14 years, respectively. There were more cases with onset in the winter and autumn, with significant peaks in February and October. From these data the prevalence of diabetes mellitus in the age group 0-14 years can be calculated to 1.2 per 1 000 children. In the whole of Norway, about 170 new cases of diabetes mellitus below the age of 15 years can be expected every year. Compared with previous studies, the present data suggest an increasing incidence of childhood diabetes in Norway.

Adolescent↗