OBJECTIVETo evaluate long-term survival, development of renal end points, and decline in glomerular filtration rate (GFR) in patients with type 2 diabetes and diabetic nephropathy (DN) after renin-angiotensin system (RAS) inhibition and multifactorial treatment of cardiovascular risk factors have become standard of care. RESEARCH DESIGN AND METHODSAll patients with type 2 diabetes and DN (n = 543) at the Steno Diabetes Center were followed during 2000-2010. GFR was measured yearly with 51 Cr-EDTA plasma clearance. Annual decline in GFR was determined in patients with at least three measurements over a minimum of 3 years (ΔGFR cohort, n = 286). Results were compared with historical data, obtained using identical criteria at our hospital, before implementation of current treatment guidelines. RESULTSBaseline mean (SD) GFR was 74 (32) mL/min/1.73 m 2 . More than 93% received RAS inhibition. During median 7.8 (interquartile range 5.7-9.8) years, mean (SE) annual GFR decline was 4.4 (0.24) compared with previously 5.2 (0.27) mL/min/ 1.73 m 2 /year (P = 0.04). Doubling of plasma creatinine or end-stage renal disease (ESRD) developed in 19%, and 37% died during 5.7 (3.3-8.8) years. Mortality from onset of DN in the ΔGFR cohort was compared with that of our prior ΔGFR cohort from 1983 to 2003 (n = 227). Crude mortality risk was reduced by 42% and after age adjustment by 50% (P < 0.001 for both). In a multistate model accounting for competing risks of ESRD and death, prior cardiovascular disease and lower GFR were predictors of mortality, whereas albuminuria, HbA 1c , and low GFR predicted ESRD. CONCLUSIONSOverall prognosis has improved considerably with current multifactorial treatment of DN in type 2 diabetes, including long-term RAS inhibition.

Summary Aims The understanding of second‐line use of glucose‐lowering drugs (GLDs) in the general population with type 2 diabetes (T2D) treatment is important as recent results have shown cardiovascular benefits with sodium‐glucose cotransporter‐2 inhibitors (SGLT‐2i) and glucagon‐like peptide‐1 receptor agonists (GLP‐1RA). Our aim was to describe second‐line GLD treatment patterns in four Nordic countries. Methods All T2D patients treated with GLD between 2006 and 2015 were identified in prescribed drug registries in Denmark, Finland, Norway and Sweden, and linked with National Patient and Cause of Death Registries. Second‐line treatment was defined as a prescription of a second GLD class following ≥6 months of metformin monotherapy. Index was the date of first dispense of the second‐line drug. Results A rapid uptake of newer GLDs (GLP‐1RA, DPP‐4i and SGLT‐2i) over the 10‐year observation period was seen in Denmark, Finland and Norway, while slower in Sweden. In 2015, 33,880 (3.1%) of 1,078,692 T2D patients initiated second‐line treatment, and newer GLDs were more commonly used in Finland (92%), Norway (71%) and Denmark (70%) vs Sweden (44%). In 2015, the use of older GLDs (insulin and sulphonylureas) was 7‐fold greater in Sweden compared to Finland (49% vs 7%), and 1.6‐fold greater compared with Denmark and Norway (49% vs 30% and 29%, respectively). Conclusions Despite comparable demography and healthcare systems in four neighbouring countries, surprisingly large differences in second‐line use of newer GLDs were found. With recent evidence of potential cardiovascular benefits with newer GLDs, such differences may have an important impact on cardiovascular outcomes.

Aims/hypothesis To study the distribution of causes of death in the Danish population, and its variation by diabetes status, sex, age and calendar year as well as the years of life lost from the specific causes of death. Methods Persons aged 30-98 years were followed from 1995 to 2008 by linkage of Danish registers. Poisson regression was used to model cause-specific mortality rates by age and calendar time for each specific cause of death, according to sex and diabetes status. The mortality rates were also modelled as a function of age and birth cohort. We computed the distribution of causes of death and years of life lost from specific causes of death due to diabetes. Results During the 14-year study period, patients with diabetes contributed 2.3 million person-years of follow-up and 124,210 deaths, whereas persons without diabetes contributed 45.1 million person-years and 648,020 deaths. The mortality was higher among individuals with diabetes, and the mortality ratio (diabetes vs no diabetes) decreased with age and for all causes and cardiovascular diseases also by calendar time. The effect of sex on the association between diabetes and mortality varied with age and cause of death. About 9 years of life were lost to diabetes at age 30 years, and 3 years at age 70 years. Conclusions/interpretation Age-specific mortality is higher among people with diabetes, and rate ratios vary with age, sex, calendar period and cause of death. The distribution of causes of death was similar for persons with and without diabetes.