Mortality trends in type 1 diabetes

WSTĘP. Celem pracy była długoterminowa ocena śmiertelności oraz jej zmian w czasie wśród 1075 pacjentów chorych na cukrzycę typu 1 (początek choroby < 18 rż., chorzy zdiagnozowani w latach 1965-1979), którzy znajdują się w rejestrze obejmującym populację Allegheny County. Ocenę przeprowadzono dnia 1 stycznia 1999 roku. MATERIAŁ I METODY. W badaniu określano śmiertelność w zależności od płci i rasy na osoborok obserwacji. Obliczono również standaryzowane wskaźniki śmiertelności. Stosowano analizę przeżycia oraz model ryzyka proporcjonalnego Coxa. Trendy czasowe oceniono, dzieląc badaną populację na 3 grupy w zależności od roku, w którym postawiono diagnozę cukrzycy (1965-1969, 1970-1974, 1975-1979). WYNIKI. Oceniano przeżycie w 972 przypadkach do dnia 1 stycznia 1999 roku (stopień potwierdzenia 90,4%). Średni czas trwania cukrzycy wynosił 25,2 &plusmn; 5,8 (SD) roku. W całej grupie badanej zmarło 170 osób. Wskaźnik śmiertelności wynosił 627 na 100 000 osobolat (95% CI: 532-728), a standaryzowany wskaźnik śmiertelności - 519 (440-602). Analiza czasu przeżycia metodą Kaplana-Meiera wykazała następujące kumulacyjne wskaźniki przeżycia: 98% po 10 latach, 92,1% po 20 latach i 79,6% po 30 latach trwania cukrzycy. Stwierdzono istotną poprawę wskaźnika przeżycia (za pomocą testu log-rank) w grupie chorych, u których cukrzycę rozpoznano w latach 1965-1969 w porównaniu z grupą chorych zdiagnozowanych pomiędzy rokiem 1975 a 1979 (p = 0,03). Śmiertelność była wyższa u pacjentów pochodzenia afrykańskiego niż u chorych rasy białej, nie obserwowano natomiast różnic między płciami. Poprawa stwierdzana w ostatnich latach dotyczyła obu grup etnicznych i obu płci. WNIOSKI. Obserwowano poprawę długoterminowego przeżycia w grupie, w której diagnozę postawiono w ostatnich latach. Poprawa ta wiąże się z wprowadzeniem oznaczania HbA1c, domowych pomiarów glikemii oraz z poprawą leczenia nadciśnienia tętniczego w latach 80.OBJECTIVES. To investigate long-term mortality and its temporal trends as of 1 January 1999 among the 1,075 patients with type 1 diabetes (onset age < 18 years, diagnosed between 1965 and 1979) who comprise the Allegheny County population- -based registry. RESEARCH DESIGN AND METHODS. Overall, sex- and race-specific mortality rates per person-year of follow- up were determined. Standardized mortality ratios were also calculated. Survival analyses and Cox proportional hazard model were also used. Temporal trends were examined by dividing the cohort into three groups by year of diagnosis (1965&#150;1969, 1970&#150;1974, and 1975&#150;1979). RESULTS. Living status of 972 cases was ascertained as of January 1, 1999 (ascertainment rate 90.4%). The mean duration of diabetes was 25.2 65.8 (SD) years. Overall, 170 deaths were observed. The crude mortality rate was 627 per 100,000 person- years (95% CI 532&#150;728) and standardized mortality ratio was 519 (440&#150;602). Life-table analyses by the Kaplan-Meier method indicated cumulative survival rates of 98.0% at 10 years, 92.1% at 20 years, and 79.6% at 30 years duration of diabetes. There was a significant improvement in the survival rate between the cohort diagnosed during 1965&#150;1969 and that diagnosed during 1975&#150;1979 by the log-rank test (P = 0.03). Mortality was higher in African-Americans than in Caucasians, but there were no differences seen by sex. The improvement in recent years was seen in both ethnic groups and sexes. CONCLUSIONS. An improvement in long-term survival was observed in the more re-cently diagnosed cohort. This improvement is consistent with the introduction of HbA1 testing, home blood glucose monitoring, and improved blood pressure therapy in the 1980s

Characterization of Highper, an ENU-induced mouse mutant with abnormal psychostimulant and stress responses

RationaleChemical mutagenesis in the mouse is a forward genetics approach that introduces random mutations into the genome, thereby providing an opportunity to annotate gene function and characterize phenotypes that have not been previously linked to a given gene.ObjectivesWe report on the behavioral characterization of Highper, an N-ethyl-N-nitrosourea (ENU)-induced mutant mouse line.MethodsHighper and B6 control mice were assessed for locomotor activity in the open field and home cage environments. Basal and acute restraint stress-induced corticosterone levels were measured. Mice were tested for locomotor response to cocaine (5, 20, 30, and 45mg/kg), methylphenidate (30mg/kg), and ethanol (0.75, 1.25, and 1.75g/kg). The rewarding and reinforcing effects of cocaine were assessed using conditioned place preference and self-administration paradigms.ResultsHighper mice are hyperactive during behavioral tests but show normal home cage locomotor behavior. Highper mice also exhibit a twofold increase in locomotor response to cocaine, methylphenidate, and ethanol and prolonged activation of the hypothalamic–pituitary–adrenal axis in response to acute stress. Highper mice are more sensitive to the rewarding and reinforcing effects of cocaine, although place preference in Highper mice appears to be significantly influenced by the environment in which the drug is administered.ConclusionsAltogether, our findings indicate that Highper mice may provide important insights into the genetic, molecular, and biological mechanisms underlying stress and the drug reward pathway.Electronic supplementary materialThe online version of this article (doi:10.1007/s00213-012-2827-5) contains supplementary material, which is available to authorized users

Estimating the Cost of Type 1 Diabetes in the U.S.: A Propensity Score Matching Method

Diabetes costs represent a large burden to both patients and the health care system. However, few studies that examine the economic consequences of diabetes have distinguished between the two major forms, type 1 and type 2 diabetes, despite differences in underlying pathologies. Combining the two diseases implies that there is no difference between the costs of type 1 and type 2 diabetes to a patient. In this study, we examine the costs of type 1 diabetes, which is often overlooked due to the larger population of type 2 patients, and compare them to the estimated costs of diabetes reported in the literature.Using a nationally representative dataset, we estimate yearly and lifetime medical and indirect costs of type 1 diabetes by implementing a matching method to compare a patient with type 1 diabetes to a similar individual without the disease. We find that each year type 1 diabetes costs this country $14.4 billion (11.5-17.3) in medical costs and lost income. In terms of lost income, type 1 patients incur a disproportionate share of type 1 and type 2 costs. Further, if the disease were eliminated by therapeutic intervention, an estimated$10.6 billion (7.2-14.0) incurred by a new cohort and $422.9 billion (327.2-519.4) incurred by the existing number of type 1 diabetic patients over their lifetime would be avoided.We find that the costs attributed to type 1 diabetes are disproportionately higher than the number of type 1 patients compared with type 2 patients, suggesting that combining the two diseases when estimating costs is not appropriate. This study and another recent contribution provides a necessary first step in estimating the substantial costs of type 1 diabetes on the U.S