The association between fasting plasma glucose variability and incident eGFR decline: evidence from two cohort studies

BACKGROUND: Glycemic variability (GV) is developing as a marker of glycemic control, which can be utilized as a promising predictor of complications. To determine whether long-term GV is associated with incident eGFR decline in two cohorts of Tehran Lipid and Glucose Study (TLGS) and Multi-Ethnic Study of Atherosclerosis (MESA) during a median follow-up of 12.2 years. METHODS: Study participants included 4422 Iranian adults (including 528 patients with T2D) aged ≥ 20 years from TLGS and 4290 American adults (including 521 patients with T2D) aged ≥ 45 years from MESA. The Multivariate Cox proportional hazard models were used to assess the risk of incident eGFR decline for each of the fasting plasma glucose (FPG) variability measures including standard deviation (SD), coefficient of variation (CV), average real variability (ARV), and variability independent of the mean (VIM) both as continuous and categorical variables. The time of start for eGFR decline and FPG variability assessment was the same, but the event cases were excluded during the exposure period. RESULTS: In TLGS participants without T2D, for each unit change in FPG variability measures, the hazards (HRs) and 95% confidence intervals (CI) for eGFR decline ≥ 40% of SD, CV, and VIM were 1.07(1.01-1.13), 1.06(1.01-1.11), and 1.07(1.01-1.13), respectively. Moreover, the third tertile of FPG-SD and FPG-VIM parameters was significantly associated with a 60 and 69% higher risk for eGFR decline ≥ 40%, respectively. In MESA participants with T2D, each unit change in FPG variability measures was significantly associated with a higher risk for eGFR decline ≥ 40%.Regarding eGFR decline ≥ 30% as the outcome, in the TLGS, regardless of diabetes status, no association was shown between FPG variability measures and risk of eGFR decline in any of the models; however, in the MESA the results were in line with those of GFR decline ≥ 40%.Using pooled data from the two cohorts we found that generally FPG variability were associated with higher risk of eGFR decline ≥ 40% only among non-T2D individuals. CONCLUSIONS: Higher FPG variability was associated with an increased risk of eGFR decline in the diabetic American population; however, this unfavorable impact was found only among the non-diabetic Iranian population.