Dynamic and Dual Effects of Glycated Hemoglobin on Estimated Glomerular Filtration Rate in Type 2 Diabetic Outpatients

Abstract

<b><i>Background:</i></b> Diabetic nephropathy is the leading cause of incident end-stage renal disease in Taiwan. Previous studies on the consistent benefits of glycemic control in diabetic nephropathy focused primarily on delaying microalbuminuria. However, this effect on glomerular filtration rate (GFR) remains controversial. This study aims to establish a model that explains the controversial effects of glycated hemoglobin (HbA<sub>1C</sub>) on GFR. <b><i>Methods:</i></b> This retrospective cohort study followed subjects with type 2 diabetes mellitus, who were enrolled between June 2006 and December 2006, for 4 years. The effects of HbA<sub>1C</sub> on estimated GFR (eGFR) were examined both cross-sectionally and longitudinally. The dual effects of HbA<sub>1C</sub> on eGFR, and how renal function interferes with these effects, were investigated. <b><i>Results:</i></b> Of the 1,992 subjects enrolled, 1,699 completed the follow-up. HbA<sub>1C</sub> was positively correlated with eGFR in the cross-sectional study (β coefficient = 1.44, 95% CI: 0.71-2.17, p = 0.0001). In the longitudinal study, higher baseline HbA<sub>1C</sub> resulted in a greater decline in eGFR. The annual eGFR decline rates were -1.89, -1.29, and -0.68 ml/min/1.73 m<sup>2</sup>/year for baseline HbA<sub>1C</sub> >9, 7 to ≤9, and ≤7%, respectively. The eGFR value was simultaneously affected by concurrent (β coefficient = 0.78, 95% CI: 0.48-1.08, p < 0.0001) and preceding HbA<sub>1C</sub> (-0.52, -0.82 to -0.23, p < 0.0001). The positive effects of concurrent HbA<sub>1C</sub> on eGFR reached statistical significance at all stages of chronic kidney disease (CKD); however, the negative effects of preceding HbA<sub>1C</sub> only applied to CKD stages 3 and 4. <b><i>Conclusions:</i></b> We developed a new model that demonstrates how preceding and concurrent HbA<sub>1C</sub> simultaneously affect eGFR in opposing ways. The dynamic effects varied among different CKD stages. The deterioration in eGFR at CKD stages 3 and 4 may be postponed by intensive glycemic control. Further prospective studies may be necessary to clarify the specific CKD stage(s) that will benefit from intensive glycemic control.