Effect of long‐term glycemic variability on estimated glomerular filtration rate decline among patients with type 2 diabetes mellitus: Insights from the Diabetic Nephropathy Cohort in Singapore

Abstract

In the present study, we examined the association between HbA1c variability and renal disease progression based on estimated glomerular filtration rate (eGFR) decline in patients with type 2 diabetes mellitus (T2DM) in Singapore. Glycemic burden and renal function were retrospectively assessed in 1628 patients in 2002–2014. Multivariable logistic regression was used to assess the relationships between HbA1c variability (expressed as HbA1c coefficient of variation [HbA1c-CV] in quartiles), HbA1c intrapersonal mean (HbA1c-IM), and eGFR decline, adjusted for baseline covariates. Among patients with relatively good glycemic control (i.e. HbA1c-IM below the median cohort value [8.0%]), HbA1c-CV Quartile 4 was associated with eGFR decline (odds ratio [OR] 1.88; 95% confidence interval [CI] 1.10–3.25). The OR for HbA1c-CV Quartile 4 was 2.20 (95% CI 1.24–3.89) after additional adjustment for HbA1c-IM. Where HbA1c-IM was above the median cohort value, HbA1c-CV Quartiles 3 and 4 were associated with eGFR decline, with ORs of 2.60 (95% CI 1.48–4.55) and 3.29 (95% CI 1.89–5.76) respectively. After further adjusting for HbA1c-IM, the ORs for Quartiles 3 and 4 were 2.69 (95% CI 1.53–4.74) and 3.51 (95% CI 1.98–6.21), respectively. Variability in HbA1c is strongly and independently associated with eGFR decline in patients with T2DM independent of mean HbA1c. The findings may highlight the importance of sustained stable glycemic control in management of diabetes mellitus. 在当前的这项研究中,我们在新加坡2型糖尿病(T2DM)患者中调查了HbA1c波动性与肾病进展(根据估算的肾小球滤过率 [eGFR] 下降情况来评估)之间的关系。 回顾性地分析了2002年至2014年期间1628例患者的血糖负荷以及肾功能。使用多因素logistic回归分析来评估校正基线协变量后的HbA1c波动性(表示为HbA1c四分位变异系数[HbA1c-CV])、个体之间的HbA1c平均数(HbA1c-IM)与eGFR下降之间的关系。 在血糖控制相对较好(亦即HbA1c-IM低于队列中位数值[8.0%])的患者中,HbA1c-CV处于第4个四分位数与eGFR下降相关(风险比[OR]为1.88;95%置信区间[CI]为1.10–3.25)。另外校正HbA1c-IM后,发现HbA1c-CV处于第4个四分位数的OR为2.20(95% CI为1.24–3.89)。在HbA1c-IM超过队列中位数值的患者中,发现HbA1c-CV处于第3以及第4个四分位数与eGFR下降相关,ORs分别为2.60(95% CI为1.48–4.55)与3.29(95% CI 1.89–5.76)。进一步校正HbA1c-IM后,发现HbA1c-CV处于第3以及第4个四分位数的ORs分别为2.69(95% CI为1.53-4.74)与3.51(95% CI为1.98-6.21)。 在T2DM患者中HbA1c的波动性与eGFR下降之间具有强烈的独立相关性并且不依赖于平均HbA1c。这项研究结果突出了糖尿病管理中持续稳定控制血糖的重要性。