title: Improved glycemic control and risk of ESRD in patients with type 1 diabetes and proteinuria.
abstract: Most patients with type 1 diabetes (T1D) and proteinuria have poor glycemic control and a high risk of ESRD. We investigated whether long-term improvement of glycemic control reduces risk of ESRD in a prospective 7- to 15-year follow-up observation of 349 patients with CKD stages 1-3 enrolled in the Joslin Proteinuria Cohort of adults with T1D. All patients developed proteinuria between 1990 and 2004 and were followed until 2011 to ascertain onset of ESRD and deaths unrelated to ESRD. Furthermore, we analyzed data from 279 patients with ≥3 years of clinic follow-up available to assess the level of glycemic control after enrollment. Average HbA1c during the 5 years before study enrollment (prebaseline) was compared with HbA1c (postbaseline) averaged during the first half of follow-up (median, 5.1 years). Median prebaseline HbA1c was 9.3%, decreasing to 8.7% postbaseline. Cumulative risk of ESRD after 15 years was significantly lower for patients whose HbA1c decreased than for those whose HbA1c increased or remained poor (29% versus 42%; P<0.001). The difference between these groups was not visible at 5 years of follow-up but became visible at 10 and 15 years of follow-up. In multivariate Cox regression analysis of ESRD risk, the hazard ratio corresponding to a 1-percentage point improvement in postbaseline HbA1c was 0.76 (95% confidence interval, 0.63 to 0.91; P=0.003). In conclusion, results of this study suggest that long-term sustained improvement in HbA1c decelerates eGFR loss and delays the onset of ESRD in patients with T1D and proteinuria.
authors.affiliation: Research and Clinic Divisions at Joslin Diabetes Center and Department of Medicine, Brigham and Women Hospital, Harvard Medical School, Boston, Massachusetts; Department of Metabolic Diseases, Jagiellonian University Medical College, Krakow, Poland;
authors.forename: Jan
authors.initials: J
authors.lastname: Skupien
authors.affiliation: Research and Clinic Divisions at Joslin Diabetes Center and.
authors.forename: James H
authors.initials: JH
authors.lastname: Warram
authors.affiliation: Research and Clinic Divisions at Joslin Diabetes Center and.
authors.forename: Adam
authors.initials: A
authors.lastname: Smiles
authors.affiliation: Institute of Gerontology, University of Michigan Medical School, Ann Arbor, Michigan; Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, Michigan; and.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Galecki
authors.affiliation: Research and Clinic Divisions at Joslin Diabetes Center and Renal Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Stanton
authors.affiliation: Research and Clinic Divisions at Joslin Diabetes Center and Department of Medicine, Brigham and Women Hospital, Harvard Medical School, Boston, Massachusetts; Andrzej.Krolewski@joslin.harvard.edu.
authors.forename: Andrzej S
authors.initials: AS
authors.lastname: Krolewski
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001786:Blood Glucose / Q000032:analysis; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000150:complications* / Q000652:urine; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000473:pathology* / Q000652:urine; D007676:Kidney Failure, Chronic / Q000097:blood / Q000473:pathology* / Q000652:urine; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011507:Proteinuria / Q000175:diagnosis*; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin
keywords: diabetes; end stage kidney disease; proteinuria