Change in Albuminuria and eGFR Following Insulin Sensitization Therapy Versus Insulin Provision Therapy in the BARI 2D Study

Abstract

SummaryBackground and objectives In the Bypass Angioplasty Revascularization Investigation 2 Diabetes randomized trial, glycemic control with insulin-sensitization therapy was compared with insulin-provision therapy in patients with type 2 diabetes and coronary artery disease. This study examined differences in albumin excretion and renal function in the insulin-sensitization group versus the insulin-provision group over 5 years.Design, setting, participants & measurements In total, 1799 patients with measurements of creatinine and urine albumin/creatinine ratio at baseline and at least two follow-up visits were included. Management of BP, lipids, and lifestyle counseling was uniform. Progression of albuminuria was defined as doubling of baseline albumin/creatinine ratio to at least 100 mg/g or worsening of albumin/creatinine ratio status on two or more visits. Worsening renal function was defined as .25% decline in estimated GFR and annualized decline of .3 ml/min per 1.73 m 2 per year.Results By 6 months and thereafter, the mean glycated hemoglobin levels were lower in the insulin-sensitization group compared with the insulin-provision group (P,0.002 for each time point; absolute difference=0.4%). Albumin/creatinine ratio increased over time in the insulin-sensitization group (P value for trend,0.001) and was stable in the insulin-provision group. Risk for progression of albumin/creatinine ratio was higher in the insulin-sensitization group compared with the insulin-provision group (odds ratio, 1.59; 95% confidence interval, 1.25 to 2.02; P=0.02). Over 5 years, albumin/creatinine ratio increased from 11.5 (interquartile range=5.0-46.7) to 15.7 mg/g (interquartile range=6.2-55.4) in the insulin-sensitization group (P,0.001) and from 12.1 (interquartile range=5.3-41.3) to 12.4 mg/g (interquartile range=5.8-50.6) in the insulin-provision group (P=0.21). Estimated GFR declined from 75.0620.6 to 66.3622.6 ml/min per 1.73 m 2 in the insulin-sensitization group (P,0.001) and from 76.1629.5 to 66.8622.1 ml/min per 1.73 m 2 in the insulin-provision group (P,0.001).Conclusion Over 5 years, despite lower glycated hemoglobin levels, the insulin-sensitization treatment group had greater progression of albumin/creatinine ratio compared with the insulin-provision treatment group. Decline in estimated GFR was similar.

Insulin Sensitivity Is an Important Determinant of Renal Health in Adolescents With Type 2 Diabetes

“…Since insulin sensitivity can be modified by both lifestyle changes (diet and exercise) and drugs such as metformin, improved insulin sensitivity holds promise as a therapeutic target to reduce DN in adolescents with type 2 diabetes. The BARI-2D study ( 33 ) showed no benefit of insulin sensitizing strategy on DN in older adults with coronary artery disease and type 2 diabetes, but with a mean age of 62 years and most participants having both hypertension and hyperlipidemia, this is a very different study population than ours ( 34 ). The renal injury in longstanding nephropathy in older adults with multiple cardiovascular risk factors may also be less responsive to changes in insulin sensitivity than the early alterations in renal function seen in adolescents with type 2 diabetes.…”

Insulin Sensitivity and Diabetic Kidney Disease in Children and Adolescents With Type 2 Diabetes: An Observational Analysis of Data From the TODAY Clinical Trial

“…metformin), IS may be a promising therapeutic target to reduce DKD in adolescents with T2D. In adults with coronary artery disease and T2D (41), BARI-2D (Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes) insulin-sensitizing therapy had no benefit on progression of DKD. However, this study population was significantly different than the TODAY cohort, with a mean participant age of 62 years and most participants already having hypertension and hyperlipidemia at baseline (42).…”

Relationship of mildly increased albuminuria and coronary artery revascularization outcomes in patients with diabetes

“…The study was approved by the Institutional Review Boards at each participating site and all participants gave written informed consent. Details of study design, characteristics of the study population, baseline kidney function, change in albuminuria following therapy, and primary outcome have been reported previously. The dataset used in this post hoc analysis was obtained from BioLINCC (The National Heart, Lung, and Blood Institute Biologic Specimen and Data Repository Information Coordinating Center) in Excel (Microsoft, Redmond, WA) format for a retrospective study based on uACR.…”