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      Increased urine IgM excretion predicts cardiovascular events in patients with type 1 diabetes nephropathy

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      1 , 2 , 2 , 2 , 2 ,
      BMC Medicine
      BioMed Central

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          Abstract

          Background

          Diabetic nephropathy, a major complication of diabetes, is characterized by progressive renal injury and increased cardiovascular mortality. An increased urinary albumin excretion due dysfunction of the glomerular barrier is an early sign of diabetic nephropathy. An increased urinary excretion of higher molecular weight proteins such as IgM appears with progression of glomerular injury. We aim here to study the prognostic significance of urine IgM excretion in patients with type 1 diabetes mellitus (type 1 diabetic nephropathy).

          Methods

          This is an observational study of 139 patients with type1 diabetes mellitus (79 males and 60 females) under routine care at the diabetic outpatient clinic at the Lund University Hospital. The median follow-up time was 18 years (1 to 22) years. Urine albumin and urine IgM concentration were measured at time of recruitment.

          Results

          Overall 32 (14 male and 18 female) patients died in a cardiovascular event and 20 (11 male and 9 female) patients reached end-stage renal disease. Univariate analysis indicated that patient survival and renal survival were inversely associated with urine albumin excretion (RR = 2.9 and 5.8, respectively) and urine IgM excretion (RR = 4.6 and 5.7, respectively). Stratified analysis demonstrated that in patients with different degrees of albuminuria, the cardiovascular mortality rate and the incidence of end-stage renal disease was approximately three times higher in patients with increased urine IgM excretion.

          Conclusion

          An increase in urinary IgM excretion in patients with type 1 diabetes is associated with an increased risk for cardiovascular mortality and renal failure, regardless of the degree of albuminuria.

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          Most cited references23

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          Incidence of end-stage renal disease in patients with type 1 diabetes.

          End-stage renal disease (ESRD) is one of the most severe complications of type 1 diabetes. Yet, data on patients' risk of developing ESRD are sparse. To estimate the long-term risk of developing ESRD and to assess how age at diagnosis of diabetes, time period of diagnosis, and sex affect the risk. A cohort of all patients younger than 30 years diagnosed as having type 1 diabetes in Finland in 1965-1999 (n = 20,005) was identified from the Finnish Diabetes Register. The cohort was followed up from diagnosis of diabetes until development of ESRD (dialysis or kidney transplantation as identified from the Finnish Registry for Kidney Diseases), death, or end of follow-up on December 31, 2001. Cumulative incidence of ESRD, accounting for death as a competing risk. The cohort was followed up for maximally 37 years, with a median of 16.7 years. During 346 851 person-years, 632 patients developed ESRD. The cumulative incidence of ESRD was 2.2% at 20 years and 7.8% at 30 years after diagnosis. The risk of developing ESRD was lowest in patients whose diagnosis occurred at younger than 5 years. The risk of ESRD was lower for patients diagnosed as having type 1 diabetes in later years. The risk did not differ significantly between sexes. With regard to ESRD, the prognosis of type 1 diabetes has improved during the past 4 decades. Children diagnosed as having diabetes before age 5 years have the most favorable prognosis. Overall, incidence of ESRD appears to be lower than previously estimated.
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            Diabetic nephropathy in 27,805 children, adolescents, and adults with type 1 diabetes: effect of diabetes duration, A1C, hypertension, dyslipidemia, diabetes onset, and sex.

            To give an up-to-date profile of nephropathy and the involvement of risk factors in a large, prospective cohort of patients with type 1 diabetes and largely pediatric and adolescent onset of disease. A total of 27,805 patients from the nationwide, prospective German Diabetes Documentation System survey were included in the present analysis. Inclusion criteria were at least two documented urine analyses with identical classification. Urine analyses, treatment regimens, diabetes complications, and risk factors were recorded prospectively. Baseline characteristics were age at diagnosis 9.94 years (median [interquartile range 5.8-14.3]), age at last visit 16.34 years (12.5-22.2), and follow-up time 2.5 years (0.43-5.3). Cumulative incidence of nephropathy was tested by Kaplan-Meier analysis and association with risk factors by logistic regression. Nephropathy was classified as normal in 26,605, microalbuminuric in 919, macroalbuminuric in 78, and end-stage renal disease (ESRD) in 203 patients. After calculated diabetes duration of 40 years, 25.4% (95% CI 22.3-28.3) had microalbuminuria and 9.4% (8.3-11.4) had macroalbuminuria or ESRD. Risk factors for microalbuminuria were diabetes duration (odds ratio 1.033, P < 0.0001), A1C (1.13, P < 0.0001), LDL cholesterol (1.003, P < 0.0074), and blood pressure (1.008, P < 0.0074), while childhood diabetes onset (1.011, P < 0.0001) was protective. Male sex was associated with the development of macroalbuminuria. Diabetes duration, A1C, dyslipidemia, blood pressure, and male sex were identified as risk factors for nephropathy. Therefore, besides the best possible metabolic control, early diagnosis and prompt treatment of dyslipidemia and hypertension is mandatory in patients with type 1 diabetes.
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              A national record linkage to study acute myocardial infarction incidence and case fatality in Sweden.

              During the last decades substantial temporal changes, as well as population differences, in coronary heart disease mortality have occurred in Sweden. There is little information to what extent these changes and differences also apply to myocardial infarction incidence. The aim of this paper was to describe the methods used to identify cases in a recently developed National Acute Myocardial Infarction Register in Sweden, and to present estimates of incidence and case fatality in Sweden. Incident cases of acute myocardial infarction (AMI) were identified by record linkage of routinely collected data on hospital discharges and deaths. Case fatality within 28 days was ascertained by linkage of incident cases to the National Cause of Death Register. About 40 000 new cases of AMI per year were recorded in Sweden during 1987-1995. Well-known differences in incidence with regard to age and gender were observed, as well as a decline in incidence between 1987 and 1995. A similar case fatality was seen in men and women aged 30-89 among hospitalized cases. When fatal cases outside hospital were also considered the case fatality was somewhat higher in men. Examination of medical records for a national sample of ischaemic heart disease patients suggested a high sensitivity (94%) and a high positive predictive value (86%) for ICD-9 code 410 in hospital discharge data with regard to definite AMI. The National Acute Myocardial Infarction Register offers a new possibility to study the incidence of AMI, as well as case fatality, in Sweden.
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                Author and article information

                Journal
                BMC Med
                BMC Medicine
                BioMed Central
                1741-7015
                2009
                4 August 2009
                : 7
                : 39
                Affiliations
                [1 ]Department of Acute Medicine, Lund University, Lund, Sweden
                [2 ]Department of Nephrology, Lund University, Lund, Sweden
                Article
                1741-7015-7-39
                10.1186/1741-7015-7-39
                2729477
                19653885
                8553cbe1-b540-41fd-9545-a2f8a638aecf
                Copyright © 2009 Tofik et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 7 July 2009
                : 4 August 2009
                Categories
                Research Article

                Medicine
                Medicine

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