Survival in type 1 diabetes has improved, but the impact on life expectancy in the U.S. type 1 diabetes population is not well established. Our objective was to estimate the life expectancy of the Pittsburgh Epidemiology of Diabetes Complications (EDC) study cohort and quantify improvements by comparing two subcohorts based on year of diabetes diagnosis (1950–1964 [n = 390] vs. 1965–1980 [n = 543]). The EDC study is a prospective cohort study of 933 participants with childhood-onset (aged <17 years) type 1 diabetes diagnosed at Children’s Hospital of Pittsburgh from 1950 to 1980. Mortality ascertainment was censored 31 December 2009. Abridged cohort life tables were constructed to calculate life expectancy. Death occurred in 237 (60.8%) of the 1950–1964 subcohort compared with 88 (16.2%) of the 1965–1980 subcohort. The life expectancy at birth for those diagnosed 1965–1980 was ∼15 years greater than participants diagnosed 1950–1964 (68.8 [95% CI 64.7–72.8] vs. 53.4 [50.8–56.0] years, respectively) (P < 0.0001); this difference persisted regardless of sex or pubertal status at diagnosis. This improvement in life expectancy emphasizes the need for insurance companies to update analysis of the life expectancy of those with childhood-onset type 1 diabetes because weighting of insurance premiums is based on outdated estimates.

Aims/hypothesis The FinnDiane Study has reported that mortality in type 1 diabetes is not increased over a 7 year follow-up in the absence of renal disease (RD). Using the Pittsburgh Epidemiology of Diabetes Complications (EDC) Study population (n = 658) of childhood-onset type 1 diabetes (age 200 μg/min), or end stage renal disease (ESRD; dialysis or renal transplantation). Results At baseline, 311 (47.3%) individuals had RD (MA 21.3%, ON 22.2% and ESRD 3.8%). During a median 20 year follow-up, there were 152 deaths (23.1%). Mortality was 6.2 (95% CI 5.2–7.2) times higher than expected, with standardised mortality ratios of 2.0 (1.2–2.8) for normoalbuminuria (NA); 6.4 (4.4–8.4) for MA; 12.5 (9.5–15.4) for ON; and 29.8 (16.8–42.9) for ESRD. Excluding those (n = 64) with NA who later progressed to RD, no significant excess mortality was observed in the remaining NA group (1.2, 0.5–1.9), whose deaths were largely unrelated to diabetes. Conclusions/interpretation These data confirm the importance of RD, including persistent microalbuminuria, as a marker of mortality risk and suggest that type 1 diabetes patients without renal disease achieve long-term survival comparable to the general population.

Precision medicine is part of the logical evolution of contemporary evidence-based medicine that seeks to reduce errors and optimize outcomes when making medical decisions and health recommendations. Diabetes affects hundreds of millions of people worldwide, many of whom will develop life-threatening complications and die prematurely. Precision medicine can potentially address this enormous problem by accounting for heterogeneity in the etiology, clinical presentation and pathogenesis of common forms of diabetes and risks of complications. This second international consensus report on precision diabetes medicine summarizes the findings from a systematic evidence review across the key pillars of precision medicine (prevention, diagnosis, treatment, prognosis) in four recognized forms of diabetes (monogenic, gestational, type 1, type 2). These reviews address key questions about the translation of precision medicine research into practice. Although not complete, owing to the vast literature on this topic, they revealed opportunities for the immediate or near-term clinical implementation of precision diabetes medicine; furthermore, we expose important gaps in knowledge, focusing on the need to obtain new clinically relevant evidence. Gaps include the need for common standards for clinical readiness, including consideration of cost-effectiveness, health equity, predictive accuracy, liability and accessibility. Key milestones are outlined for the broad clinical implementation of precision diabetes medicine.

Significance Statement: Although studies show that diabetic kidney disease has a heritable component, searches for the genetic determinants of this complication of diabetes have had limited success. In this study, a new international genomics consortium, the JDRF funded Diabetic Nephropathy Collaborative Research Initiative, assembled nearly 20,000 samples from participants with type 1 diabetes, with and without kidney disease. The authors found 16 new diabetic kidney disease–associated loci at genome-wide significance. The strongest signal centers on a protective missense coding variant at COL4A3, a gene that encodes a component of the glomerular basement membrane that, when mutated, causes the progressive inherited nephropathy Alport syndrome. These GWAS-identified risk loci may provide insights into the pathogenesis of diabetic kidney disease and help identify potential biologic targets for prevention and treatment. Background: Although diabetic kidney disease demonstrates both familial clustering and single nucleotide polymorphism heritability, the specific genetic factors influencing risk remain largely unknown. Methods: To identify genetic variants predisposing to diabetic kidney disease, we performed genome-wide association study (GWAS) analyses. Through collaboration with the Diabetes Nephropathy Collaborative Research Initiative, we assembled a large collection of type 1 diabetes cohorts with harmonized diabetic kidney disease phenotypes. We used a spectrum of ten diabetic kidney disease definitions based on albuminuria and renal function. Results: Our GWAS meta-analysis included association results for up to 19,406 individuals of European descent with type 1 diabetes. We identified 16 genome-wide significant risk loci. The variant with the strongest association (rs55703767) is a common missense mutation in the collagen type IV alpha 3 chain (COL4A3) gene, which encodes a major structural component of the glomerular basement membrane (GBM). Mutations in COL4A3 are implicated in heritable nephropathies, including the progressive inherited nephropathy Alport syndrome. The rs55703767 minor allele (Asp326Tyr) is protective against several definitions of diabetic kidney disease, including albuminuria and ESKD, and demonstrated a significant association with GBM width; protective allele carriers had thinner GBM before any signs of kidney disease, and its effect was dependent on glycemia. Three other loci are in or near genes with known or suggestive involvement in this condition (BMP7) or renal biology (COLEC11 and DDR1). Conclusions: The 16 diabetic kidney disease–associated loci may provide novel insights into the pathogenesis of this condition and help identify potential biologic targets for prevention and treatment.