BACKGROUND: The SEL1L gene is located on human chromosome 14q24.3-31 close to D14S67 which has been previously proposed to be a type 1 diabetes mellitus locus (IDDM11). Sel-1 is a negative regulator of the Notch signalling pathway and SEL1L is selectively expressed in adult pancreas and islets of Langerhans. This suggests that SEL1L may be a candidate gene for IDDM11. METHODS: We have analysed two newly identified CA-repeat polymorphisms within the genomic sequence of the SEL1L locus for association with type 1 diabetes mellitus (T1DM) in 152 Danish T1DM-affected sib-pair families and in 240 Sardinian families (229 simplex and 11 sib-pair families). RESULTS: No evidence for association of the two SEL1L markers with T1DM was observed in either the Danish or the Sardinian families. We have also used allelic sharing methods to analyse linkage with T1DM in the IDDM11 region using the same markers and the Danish collection of affected sib-pair families. No evidence of linkage was observed (Z(max)=0.86). CONCLUSION: Although several lines of evidence suggest that SEL1L might be a candidate for IDDM11-conferred susceptibility to T1DM the present study does not support this hypothesis.

Alleles↗

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Plasma growth hormone and hypertrophic osteoarthropathy in carcinoma of the bronchus.

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Aged↗

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The natural history of insulin-dependent diabetes mellitus in Denmark: 1. Long-term survival with and without late diabetic complications.

All 906 patients with insulin-dependent diabetes mellitus (IDDM) diagnosed before the age of 31 years, prior to 1943, and admitted to the Steno Memorial Hospital were followed until death or until 1 January 1984. In an attempt to identify factors of prognostic importance, we compared patients dying within 35 years of the onset of diabetes with patients surviving for 40 years or more. Three hundred and seventy-seven patients survived for 40 years or more; of these 224 were still alive and invited to a re-examination, in which 184 participated. After 40 years of diabetes, the most frequent complications were impaired vision (due to diabetic retinopathy) and persistent proteinuria. However, 53% had no major complications despite 40 years with IDDM. The 184 re-examined patients (median age 60 years, median diabetes duration 47 years) were all genuine IDDM patients, as defined by stimulated C-peptide levels. Proliferative retinopathy or visual impairment was found in 56% of the 184 patients, abnormal ECG or amputations in 26%, and elevated urinary albumin excretion rate (AER) greater than or equal to 30 mg/24 h) in 45%. Twenty-five per cent had none of these complications. Proliferative retinopathy was associated with elevated AER and raised systolic blood pressure, macroangiopathy with the use of antihypertensive drugs, and proteinuria with low age at diagnosis, large increase in systolic blood pressure, smoking, and insulin-binding antibodies. Sex, age and diabetes duration were not associated with any of these three late diabetic complications.

Adolescent↗

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The natural history of insulin-dependent diabetes in Denmark: 2. Long-term survival--who and why.

Forty per cent of all Danish insulin-dependent diabetic (IDDM) patients survive for at least 40 years after diagnosis. In an attempt to identify factors influencing the probability of surviving for 40 years or more, we followed all IDDM patients diagnosed before 1943 and admitted to the Steno Memorial Hospital. Patients surviving greater than or equal to 40 years were compared with patients dying within 35 years of diabetes diagnosis. Patients dying within 35 years were characterized by male preponderance (p less than 0.01), poor metabolic control (p less than 0.05), and by less frequent attendance at a specialized care unit (p less than 0.0001). Death due to uraemia/diabetic nephropathy was also characterized by male preponderance, poor metabolic control, and few contacts with a specialized care unit but in patients dying from cardiovascular disease (CVD), no effect of sex was found, indicating that the protection from CVD found in the female non-diabetic population is absent in IDDM patients. We conclude that long-term survival with IDDM may be determined by factors susceptible to intervention such as metabolic regulation and patient attitude to their disease.

Adult↗

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Incidence of insulin-dependent diabetes mellitus in age groups over 30 years in Denmark.

The incidence of IDDM in the age group over 30 years was estimated in a historical prospective study, using clinical and biochemical measurements at onset as criteria for classification. The study population, nearly one million, represents 20% of the Danish population. The degree of ascertainment was > 99%. One thousand two hundred and forty patients were treated with insulin during the study period (1973-77). Based on the clinical and biochemical variables, the patients were classified into three groups: insulin-dependent diabetes mellitus (IDDM) accounted for 16.2%, insulin-treated diabetes mellitus for 54.1% and short-term treated diabetes mellitus for 29.6% of the total insulin-treated group. The incidence of IDDM in the age group over 30 years at onset was 8.2 100,000(-1) year-1. The cumulative incidence rate (0-90 years) was 1.5-1.6 per cent. The present study indicates that IDDM may develop at any age. Thus the life-time risk of developing IDDM is higher than hitherto expected.

Adult↗