Abstract
ObjectiveEstimation of glomerular filtration rate (eGFR) is one of the current clinical methods for identifying risk for diabetic nephropathy in subjects with type 1 diabetes (T1D). Hyperglycemia is known to influence GFR in T1D and variability in blood glucose at the time of eGFR measurement could introduce bias in eGFR. We hypothesized that simultaneously measured blood glucose would influence eGFR in adults with T1D.MethodsLongitudinal multivariable mixed-models were employed to investigate the relationships between blood glucose and eGFR by CKD-EPI eGFRCYSTATIN C over 6-years in the Coronary Artery Calcification in Type 1 diabetes (CACTI) study. All subjects with T1D and complete data including blood glucose and cystatin C for at least one of the three visits (n = 616, 554, and 521, respectively) were included in the longitudinal analyses.ResultsIn mixed-models adjusting for sex, HbA1c, ACEi/ARB, protein and sodium intake positive associations were observed between simultaneous blood glucose and eGFRCYSTATIN C (β±SE:0.14±0.04 per 10 mg/dL of blood glucose, p<0.0001), and hyperfiltration as a dichotomous outcome (OR: 1.04, 95% CI: 1.01–1.07 per 10 mg/dL of blood glucose, p = 0.02).ConclusionsIn our longitudinal data in subjects with T1D, simultaneous blood glucose has an independent positive effect on eGFRCYSTATIN C. The associations between blood glucose and eGFRCYSTATIN C may bias the accurate detection of early diabetic nephropathy, especially in people with longitudinal variability in blood glucose.
Highlights
Diabetic nephropathy (DN) remains the single most important cause of renal failure in North America, and one of the major causes of mortality in type 1 diabetes [1,2]
The influence of simultaneous blood glucose on estimated glomerular filtration rate (eGFR) was suggested by the DCCT-EDIC study which showed a decrease of 4.2 mL/min/1.73 m2 in eGFR from baseline to year one among subjects randomized to intensive diabetes control and a sustained lower eGFR during the DCCT; eGFR decreased 4.8 mL/min/1.73 m2 from DCCT close-out to year 1 of EDIC in subjects in the conventional arm after transition to more intensive diabetes management [12]
Compared to creatinine-based equations, we have previously demonstrated that cystatin C has a superior ability to experimentally detect acute changes in GFR induced by hyperglycemia under carefully controlled physiological conditions [14]
Summary
Diabetic nephropathy (DN) remains the single most important cause of renal failure in North America, and one of the major causes of mortality in type 1 diabetes [1,2]. The effect of hyperglycemia on renal physiology and GFR measurement is well recognized in controlled studies [7,8], but is not accounted for in GFR estimating equations, which could introduce bias in the 1.5 million patients in the US and 20 million worldwide with type 1 diabetes (T1D) [9,10,11]. EGFR equations have included subjects with T1D [6], only diabetes status was considered and not blood glucose concentrations as potential explanatory variables. The influence of simultaneous blood glucose on eGFR (using serum creatinine) was suggested by the DCCT-EDIC study which showed a decrease of 4.2 mL/min/1.73 m2 in eGFR from baseline to year one among subjects randomized to intensive diabetes control and a sustained lower eGFR during the DCCT; eGFR decreased 4.8 mL/min/1.73 m2 from DCCT close-out to year 1 of EDIC in subjects in the conventional arm after transition to more intensive diabetes management [12]. Over 6 K years in the DCCT the overall difference in mean daytime blood glucose between intensively and conventionally treated subjects was 76 mg/dL and associated with a
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