Aims/hypothesis: We examined long-term total and cause-specific mortality in a nationwide, populationbased Norwegian cohort of patients with childhood-onset type 1 diabetes. Materials and methods: All Norwegian type 1 diabetic patients who were diagnosed between 1973 and 1982 and were under 15 years of age at diagnosis were included (n=1,906). Mortality was recorded from diabetes onset until 31 December 2002 and represented 46,147 person-years. The greatest age attained among deceased subjects was 40 years and the maximum diabetes duration was 30 years. Cause of death was ascertained by reviews of death certificates, autopsy protocols and medical records. The standardised mortality ratio (SMR) was based on national background statistics. Results: During follow-up 103 individuals died. The mortality rate was 2.2/1000 person-years. The overall SMR was 4.0 (95% CI 3.2-4.8) and was similar for males and females. For ischaemic heart disease the SMR was 20.2 (7.3-39.8) for men and 20.6 (1.8-54.1) for women. Acute metabolic complications of diabetes were the most common cause of death under 30 years of age (32%). Cardiovascular disease was responsible for the largest proportion of deaths from the age of 30 years onwards (30%). Violent death accounted for 28% of the deaths in the total cohort (35% among men and 11% among women). Conclusions/interpretation: Childhood-onset type 1 diabetes still carries an increased mortality risk when compared with the general population, particularly for cardiovascular disease. To reduce these deaths, attention should be directed to the prevention of acute metabolic complications, the identification of psychiatric vulnerability and the early detection and treatment of cardiovascular disease and associated risk factors.

The Diabetes Virus Detection study (DiViD) is the first to examine fresh pancreatic tissue at the diagnosis of type 1 diabetes for the presence of viruses. Minimal pancreatic tail resection was performed 3–9 weeks after onset of type 1 diabetes in six adult patients (age 24–35 years). The presence of enteroviral capsid protein 1 (VP1) and the expression of class I HLA were investigated by immunohistochemistry. Enterovirus RNA was analyzed from isolated pancreatic islets and from fresh-frozen whole pancreatic tissue using PCR and sequencing. Nondiabetic organ donors served as controls. VP1 was detected in the islets of all type 1 diabetic patients (two of nine controls). Hyperexpression of class I HLA molecules was found in the islets of all patients (one of nine controls). Enterovirus-specific RNA sequences were detected in four of six patients (zero of six controls). The results were confirmed in various laboratories. Only 1.7% of the islets contained VP1+ cells, and the amount of enterovirus RNA was low. The results provide evidence for the presence of enterovirus in pancreatic islets of type 1 diabetic patients, which is consistent with the possibility that a low-grade enteroviral infection in the pancreatic islets contributes to disease progression in humans.

In a study of retinopathy during one year of tight blood glucose control 45 type I (insulin dependent) diabetics without proliferative retinopathy were randomised to receive either continuous subcutaneous insulin infusion, multiple insulin injections, or conventional insulin treatment (controls). Near

Forty five insulin dependent diabetics were randomised to treatment with continuous subcutaneous insulin infusion (CSII), multiple insulin injections (five or six daily), or conventional twice daily insulin injections. Near normoglycaemia was obtained with CSII and multiple injections but not with conventional treatment (p

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Aims/hypothesis AGEs, modification products formed by glycation or glycoxidation of proteins and lipids, have been linked to premature atherosclerosis in patients with diabetes. We investigated whether increased serum levels of AGEs predict total, cardiovascular (CVD) or CHD mortality in a population-based study. Subjects and methods Serum levels of AGEs were determined by immunoassay in a random sample of 874 Finnish diabetic study participants (488 men, 386 women), aged 45-64 years. These participants were followed for 18 years for total, CVD and CHD mortality. Results Multivariate Cox regression models revealed that serum levels of AGEs were significantly associated with total (p=0.002) and CVD mortality (p=0.021) in women, but not in men. Serum levels of AGEs in the highest sexspecific quartile predicted all-cause (hazards ratio [HR] 1.51; 95% confidence intervals [CI], 1.14-1.99; p=0.004), CVD (HR 1.56; 95% CI 1.12-2.19; p=0.009), and CHD (HR 1.68; 95% CI 1.11-2.52; p=0.013) mortality in women, even after adjustment for confounding factors, including high-sensitivity C-reactive protein. Conclusions/interpretation

Increased serum levels of AGEs, unlike serum levels of CML, are associated with heart stiffness in patients with type 1 diabetes, possibly mediated by the cross-linking properties of AGEs.

Type 1 diabetic patients have a pronounced risk of premature coronary artery disease and death. We sought to evaluate the prevalence of silent coronary atheromatosis and to evaluate the relation between coronary atheromatosis and glycemic control. Coronary atheromatosis was evaluated in type 1 diabetic patients with no symptoms of coronary artery disease by exercise electrocardiogram (ECG) in 39 patients and quantitative coronary angiography and by intravascular ultrasound (IVUS) examinations in 29 patients. The findings from the IVUS examinations were related to mean HbA 1c collected prospectively over 18 years. Abnormal exercise ECGs were found in 15% of patients, and angiographic diameter stenosis of >50% in one or more of the main coronary arteries was found in 34% of patients. All patients examined with intracoronary ultrasound had developed atherosclerotic plaques with an increased intimal thickness (>0.5 mm) in one or more of the coronary arteries. Coronary artery plaque formation, as judged by ultrasound, was significantly related to mean HbA 1c during 18 years (P < 0.05) after adjustment for total cholesterol and age. This study demonstrates a high prevalence of silent coronary atheromatosis in type 1 diabetic patients with no symptoms of coronary heart disease. Long-term glycemic control was shown to be associated with coronary atheromatosis.