Regression of albuminuria and its association with incident cardiovascular outcomes and mortality in type 1 diabetes: the FinnDiane Study

Aims/hypothesis Our aim was to assess regression of albuminuria and its clinical consequences in type 1 diabetes. Methods The analysis included 3642 participants from the Finnish Diabetic Nephropathy (FinnDiane) Study with a 24 h urine sample and a history of albuminuria available at baseline. A total of 2729 individuals had normal AER, 438 a history of microalbuminuria and 475 a history of macroalbuminuria. Regression was defined as a change from a higher category of albuminuria pre-baseline to a lower category in two out of the three most recent urine samples at baseline. The impact of regression on cardiovascular events (myocardial infarction, stroke, coronary procedure) and mortality was analysed over a follow-up of 14.0 years (interquartile range 11.9-15.9). Results In total, 102 (23.3%) individuals with prior microalbuminuria and 111 (23.4%) with prior macroalbuminuria had regressed at baseline. For individuals with normal AER as a reference, the age-adjusted HRs (95% CI) for cardiovascular events were 1.42 (0.75, 2.68) in individuals with regression from microalbuminuria, 2.62 (1.95, 3.54) in individuals with sustained microalbuminuria, 3.15 (2.02, 4.92) in individuals with regression from macroalbuminuria and 5.49 (4.31, 7.00) in individuals with sustained macroalbuminuria. Furthermore, for all-cause and cardiovascular mortality rates, HRs in regressed individuals were comparable with those with sustained renal status at the achieved level (i.e. those who did not regress but remained at the most advanced level of albuminuria noted pre-baseline). Conclusions/interpretation Progression of diabetic nephropathy confers an increased risk for cardiovascular disease and premature death. Notably, regression reduces the risk to the same level as for those who did not progress.Peer reviewe

Soluble receptor for AGE in diabetic nephropathy and its progression in Finnish individuals with type 1 diabetes

Aims/hypothesisActivation of the receptor for AGE (RAGE) has been shown to be associated with diabetic nephropathy. The soluble isoform of RAGE (sRAGE) is considered to function as a decoy receptor for RAGE ligands and thereby protects against diabetic complications. A possible association between sRAGE and diabetic nephropathy is still, however, controversial and a more comprehensive analysis of sRAGE with respect to diabetic nephropathy in type 1 diabetes is therefore warranted.MethodssRAGE was measured in baseline serum samples from 3647 participants with type 1 diabetes from the nationwide multicentre Finnish Diabetic Nephropathy (FinnDiane) Study. Associations between sRAGE and diabetic nephropathy, as well as sRAGE and diabetic nephropathy progression, were evaluated by regression, competing risks and receiver operating characteristic curve analyses. The non-synonymous SNP rs2070600 (G82S) was used to test causality in the Mendelian randomisation analysis.ResultsBaseline sRAGE concentrations were highest in participants with diabetic nephropathy, compared with participants with a normal AER or those with microalbuminuria. Baseline sRAGE was associated with progression from macroalbuminuria to end-stage renal disease (ESRD) in the competing risks analyses, but this association disappeared when eGFR was entered into the model. The SNP rs2070600 was strongly associated with sRAGE concentrations and with progression from macroalbuminuria to ESRD. However, Mendelian randomisation analysis did not support a causal role for sRAGE in progression to ESRD.Conclusions/interpretationsRAGE is associated with progression from macroalbuminuria to ESRD, but does not add predictive value on top of conventional risk factors. Although sRAGE is a biomarker of diabetic nephropathy, in light of the Mendelian randomisation analysis it does not seem to be causally related to progression from macroalbuminuria to ESRD.</p

Frequent physical activity is associated with reduced risk of severe diabetic retinopathy in type 1 diabetes

AimsThe aim of this study was to investigate whether leisure-time physical activity (LTPA) is associated with the development of severe diabetic retinopathy in individuals with type 1 diabetes.MethodsProspective observational analysis as part of the Finnish diabetic nephropathy (FinnDiane) Study with a mean follow-up time of 10.7 years was performed. A total of 1612 individuals with type 1 diabetes were recruited, and LTPA was assessed at baseline using a validated self-report questionnaire. Severe diabetic retinopathy was defined as the initiation of laser treatment due to severe nonproliferative, proliferative retinopathy or diabetic maculopathy (identified from the Care Register for Health Care).ResultsA total of 261 patients received laser treatment during the follow-up. Higher frequency of LTPA was associated with a lower incidence of severe diabetic retinopathy (p = 0.024), a finding that remained significant after adjustment for gender, duration, age at onset of diabetes, kidney function, BMI, triglycerides and systolic blood pressure. However, when HbA1c and smoking were added to the Cox regression model the association was no more significant.ConclusionsFrequent LTPA is associated with a lower incidence of severe diabetic retinopathy during the follow-up. The total amount or the other components of LTPA (intensity or duration of a single session) were not associated with severe diabetic retinopathy.</p