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OBJECTIVE-- Although management of type 1 diabetes improved dramatically in the 1980s, the effect on mortality is not clear. RESEARCH DESIGN AND METHODS-- We report trends in 30-year mortality using the Allegheny County (Pennsylvania) childhood-onset (age <18 years) type 1 diabetes registry (n = 1,075) with diagnosis from 1965-1979, by dividing the cohort into three diagnosis year cohorts (1965-1969, 1970-1974, and 1975-1979). Local (Allegheny County) mortality data were used to calculate standardized mortality ratios (SMRs). RESULTS-- As of 1 January 2008, vital status was ascertained for 97.0% of participants (n = 1,043) when mean age ± SD and duration of diabetes were 42.8 ± 8.0 and 32.0 ± 7.6 years, respectively. The 279 deaths (26.0%) observed were 7 times higher than expected (SMR 6.9 [95% CI 6.1-7.7]). An improving trend in SMR was seen by diagnosis cohort at 30 years of diabetes duration (9.3 [7.2-11.3], 7.5 [5.8 -9.2], and 5.6 [4.0 -7.2] for 1965-1969, 1970-1974, and 1975-1979, respectively). Although no sex difference in survival was observed (P = 0.27), female diabetic patients were 13 times more likely to die than age-matched women in the general population (SMR 13.2 [10.7-15.7]), much higher than the SMR for men (5.0 [4.0-6.0]). Conversely, whereas 30-year survival was significantly lower in African Americans than in Caucasians (57.2 vs. 82.7%, respectively; P < 0.001), no differences in SMR were seen by race. CONCLUSIONS-- Although survival has clearly improved, those with diabetes diagnosed most recently (1975-1979) still had a mortality rate 5.6 times higher than that seen in the general population, revealing a continuing need for improvements in treatment and care, particularly for women and African Americans with type 1 diabetes. [ABSTRACT FROM AUTHOR]

Examines the diagnosis of insulin dependent diabetes in patient with non-diabetic family members in Pittsburgh, Pennsylvania. Deviation in growth; Consistency of the predictable stage; Difference on the degree of weight loss.

Context: Though the long-term consequences of celiac disease (CD) in type 1 diabetes are unclear, CD has been associated with increased prevalence of end-stage renal disease (ESRD) independent of type 1 diabetes., Objective: We evaluated whether celiac autoimmunity is related to the cumulative incidence of microalbuminuria [albumin excretion rate (AER) 20 to 200 µg/min], macroalbuminuria (AER >200 µg/min), and ESRD., Design, Patients, and Methods: In the prospective follow-up of the Pittsburgh Epidemiology of Diabetes Complications study of childhood-onset type 1 diabetes, 618 participants were screened for tissue transglutaminase (tTG) antibodies with a clinical assay. Nephropathy outcomes were determined at 25 years of diabetes duration., Results: Overall, the 33 subjects (5.3%) with strongly positive tTG levels (≥3 times the upper limit of normal) or a reported clinical history of CD had lower baseline blood pressure and lipid values. At 25 years of diabetes duration, a lower cumulative incidence of macroalbuminuria in strongly positive subjects compared with those with negative serology (3.6% vs 30.0%; P = 0.003) remained significant after adjustment for age, HbA1c, lipid measures, and blood pressure (adjusted P = 0.004). No considerable differences between these subjects and tTG-negative groups were found for microalbuminuria (40.0% vs 57.1%) or ESRD (0 vs 4.1%)., Conclusions: These findings show that strongly positive celiac autoimmunity status in individuals with childhood-onset type 1 diabetes is associated with lower baseline blood pressure and cholesterol measurements as well as lower macroalbuminuria risk after 25 years of type 1 diabetes duration with no increase in the risk of microalbuminuria or ESRD.

Aims/hypothesis: Multiple islet autoimmunity increases risk of diabetes, but not all individuals positive for two or more islet autoantibodies progress to disease within a decade. Major islet autoantibodies recognise insulin (IAA), GAD (GADA), islet antigen-2 (IA-2A) and zinc transporter 8 (ZnT8A). Here we describe the baseline characteristics of a unique cohort of 'slow progressors' (n = 132) who were positive for multiple islet autoantibodies (IAA, GADA, IA-2A or ZnT8A) but did not progress to diabetes within 10 years., Methods: Individuals were identified from five studies (BABYDIAB, Germany; Diabetes Autoimmunity Study in the Young [DAISY], USA; All Babies in Southeast Sweden [ABIS], Sweden; Bart's Oxford Family Study [BOX], UK and the Pittsburgh Family Study, USA). Multiple islet autoantibody characteristics were determined using harmonised assays where possible. HLA class II risk was compared between slow progressors and rapid progressors (n = 348 diagnosed <5 years old from BOX) using the χ 2 test., Results: In the first available samples with detectable multiple antibodies, the most frequent autoantibodies were GADA (92%), followed by ZnT8A (62%), IAA (59%) and IA-2A (41%). High risk HLA class II genotypes were less frequent in slow (28%) than rapid progressors (42%, p = 0.011), but only two slow progressors carried the protective HLA DQ6 allele., Conclusion: No distinguishing characteristics of slow progressors at first detection of multiple antibodies have yet been identified. Continued investigation of these individuals may provide insights into slow progression that will inform future efforts to slow or prevent progression to clinical diabetes.

Objective: Little is known concerning the primary cause(s) of mortality in type 1 diabetes responsible for the excess mortality seen in this population., Research Design and Methods: The Allegheny County (Pennsylvania) childhood-onset (age < 18 years) type 1 diabetes registry (n = 1,075) with diagnosis from 1965 to 1979 was used to explore patterns in cause-specific mortality. Cause of death was determined by a mortality classification committee of at least three physician epidemiologists, based on the death certificate and additional records surrounding the death., Results: Vital status for 1,043 (97%) participants was ascertained as of 1 January 2008, revealing 279 (26.0%) deaths overall (141 females and 138 males). Within the first 10 years after diagnosis, the leading cause of death was acute diabetes complications (73.6%), while during the next 10 years, deaths were nearly evenly attributed to acute (15%), cardiovascular (22%), renal (20%), or infectious (18%) causes. After 20 years' duration, chronic diabetes complications (cardiovascular, renal, or infectious) accounted for >70% of all deaths, with cardiovascular disease as the leading cause of death (40%). Women (P < 0.05) and African Americans (P < 0.001) have significantly higher diabetes-related mortality rates than men and Caucasians, respectively. Standardized mortality ratios (SMRs) for non-diabetes-related causes do not significantly differ from the general population (violent deaths: SMR 1.2, 95% CI 0.6-1.8; cancer: SMR 1.2, 0.5-2.0)., Conclusions: The excess mortality seen in type 1 diabetes is almost entirely related to diabetes and its comorbidities but varies by duration of diabetes and particularly affects women and African Americans.

Declining incidences in Europe of overt nephropathy, proliferative retinopathy, and mortality in type 1 diabetes have recently been reported. However, comparable data for the U.S. and trend data for neuropathy and macrovascular complications are lacking. These issues are addressed using the prospective observational Pittsburgh Epidemiology of Childhood-Onset Diabetes Complications Study. Participants were stratified into five cohorts by diagnosis year: 1950-1959, 1960-1964, 1965-1969, 1970-1974, and 1975-1980. Mortality, renal failure, and coronary artery disease (CAD) status were determined on the complete cohort (n = 906) at 20, 25, and 30 years. Overt nephropathy, proliferative retinopathy, and neuropathy were assessed at 20 and 25 years on the subset of participants with a clinical examination. There was a decreasing trend by diagnosis year for mortality, renal failure, and neuropathy across all time intervals (P < 0.05), with the 1950-1959 cohort having a fivefold higher mortality at 25 years than the 1970s' cohorts. Proliferative retinopathy and overt nephropathy showed nonsignificant declines at 20 years (P < 0.16 and P < 0.13, respectively) and no change at 25 years. CAD event rates, which were lower than the other complications, also showed no trend. Although some type 1 diabetes complications (mortality, renal failure, and neuropathy) are declining, others (CAD, overt nephropathy, and proliferative retinopathy) show less favorable changes by 30 years.

Objective: The aim of this study was to compare the prevalence of being overweight in black and white children and adolescents at onset of insulin-treated diabetes during two time periods: 1979-1989 (period I) and 1990-1998 (period II)., Research Design and Methods: All black children <19 years of age diagnosed with diabetes and treated with insulin at onset admitted to the Children's Hospital of Pittsburgh between January 1979 and December 1998 were matched with white children by sex, age at onset, and year of diagnosis. Data were obtained from a review of medical records. Overweight was defined as BMI >or=85th percentile for age and sex. Islet cell autoantibodies were measured., Results: The prevalence of being overweight increased from 12.6% (period I) to 36.8% (period II) (P = 0.0003); in whites from 2.9 to 16.6% (P = 0.04) and in blacks from 22 to 55% (P = 0.001); and in the age-group <11 years from 7.3 to 22.2% (P = 0.04) and age 11-18 years from 20 to 50% (P = 0.006). In children with at least one antibody, the prevalence of being overweight increased from 5.1 to 24.4% (P = 0.001). In the multivariate logistic regression, period of diagnosis (period II), race (black), age at onset (>or=11 years old), and absence of autoimmunity were associated with being overweight., Conclusions: At onset of the disease, the prevalence of being overweight has tripled from the 1980s to the 1990s, following the trend in the general population. Weight gain may be an accelerating factor for onset of insulin-treated diabetes and may have contributed to the increased incidence of diabetes in youth seen in some populations.

Background: Little information is available regarding the long-term incidence of end-stage renal disease (ESRD) and survival after the introduction of renal replacement therapy (RRT) in patients with type 1 diabetes., Methods: We studied 1,075 patients with type 1 diabetes (onset age < 18 years) diagnosed between 1965 and 1979, who comprise the Allegheny County population-based registry. Onset of ESRD was defined as the introduction of RRT (dialysis or transplantation)., Results: Of 1,075 registrants, the living status of 975 patients (90.7%) and complication status of 798 patients (74.2%) were ascertained as of January 1, 1999. During the observation period, 104 patients (13.0%) developed ESRD, for an incidence rate of 521/100,000 person-years (95% confidence interval, 424 to 629). The cumulative incidence of ESRD was 11.3% at 25 years of diabetes. A significant decline was observed in 20-year cumulative incidence rates of ESRD for patients diagnosed between 1965 and 1969, 1970 and 1974, and 1975 and 1979 (9.1%, 4.7%, and 3.6%, respectively; P = 0.006). Of 104 patients with ESRD, 29 patients (28%) received dialysis alone, 44 patients (42%) received dialysis followed by kidney transplantation, 26 patients (25%) underwent successful transplantation alone, and 5 patients (5%) underwent a failed kidney transplantation followed by dialysis therapy. The cumulative survival rate 10 years after the introduction of RRT was 51.2%. The cumulative survival rate of dialysis therapy followed by kidney transplantation was significantly greater than that of dialysis therapy alone (P < 0.001). No difference was detected in survival between pancreas-kidney transplant recipients and kidney-alone transplant recipients (P = 0.7)., Conclusion: The incidence of ESRD observed in this cohort has declined, probably reflecting the better glycemic and blood pressure control available since the early 1980s.