Albuminuria Regression and All-Cause Mortality among Insulin-Treated Patients with Type 2 Diabetes: Analysis of a Large UK Primary Care Cohort

Abstract

Background: Overt albuminuria (urinary albumin-creatinine ratio [ACR] > 300 mg/g) is an established risk factor for progression of nephropathy and total mortality. However, whether a reduction in ACR translates into a reduction in mortality and/or cardiovascular (CV) events among insulin-treated patients with type 2 diabetes (T2D) in routine practice is currently not known. Methods: We obtained data on a large cohort of insulin users with T2D and nephropathy (baseline ACR ≥300 mg/g) from UK general practices between 2007 and 2014. Their corresponding ACR values after 1year of follow-up were thereafter categorized into: (1) < 300 mg/g (i.e., albuminuria regression) or (2) > 300 mg/g (i.e., nonregression of albuminuria), and the cohort was followed-up for 5 years for all-cause mortality and CV events. Cox proportional hazard models were fitted to estimate the risk of all-cause death. Results: A total of 11,074 patients with insulin-treated T2D met the inclusion criteria. Their mean age was 62.3 (13.6) years; mean HbA1c: 8.7 (1.8) and 53% were male. A total of 682 deaths occurred after a follow-up period of 43,393 person-years with a mortality rate of 16 per 1,000 person-years. Five-year survival was markedly reduced in the group whose proteinuria persisted or progressed (91 vs. 95%; log-rank p value < 0.001). Compared to patients whose ACR levels remained above 300 mg/g, all-cause mortality and CV events were 31 and 27% lower in those whose albuminuria regressed to < 300 mg/g (adjusted hazard ratio [aHR] 0.69; 95% CI 0.52–0.91; p = 0.008 and aHR 0. 73; 95% CI 0.54–0.98; p = 0.041), respectively. Conclusion: In patients with insulin-treated T2D and nephropathy in routine practice, a regression in albuminuria (e.g., via better BP or glycemic control) is associated with a significant reduction in all-cause mortality. Thus, albuminuria is not only simply a risk marker of renal and CV disease but also an independent target for therapy. Albuminuria reduction should be viewed as a goal for renal and CV protection.