Glycated hemoglobin and the risk of kidney disease and retinopathy in adults with and without diabetes

Abstract

Objective: Glycated hemoglobin was recently recommended for use as a diagnostic test for diabetes. We examined the association between 2010 American Diabetes Association diagnostic cut points for glycated hemoglobin and microvascular outcomes (chronic kidney disease, end-stage renal disease [ESRD], and retinopathy) and formally tested for the presence of risk thresholds in the relationships of glycated hemoglobin with these outcomes.

Research design and methods: Prospective cohort and cross-sectional analyses of 11,357 participants (773 with a history of diagnosed diabetes) from the Atherosclerosis Risk in Communities (ARIC) Study.

Results: During a median of 14 years of follow-up of individuals without diagnosed diabetes at baseline, clinical categories of glycated hemoglobin were associated with risk of chronic kidney disease, with adjusted hazard ratios (HRs) of 1.12 (0.94-1.34) and 1.39 (1.04-1.85) for glycated hemoglobin 5.7-6.4% and ≥6.5%, respectively, as compared with <5.7% (P trend = 0.002). The corresponding HRs for ESRD were 1.51 (0.82-2.76) and 1.98 (0.83-4.73), respectively (P trend = 0.047). In the absence of diagnosed diabetes, glycated hemoglobin was cross sectionally associated with the presence of moderate/severe retinopathy, with adjusted odds ratios of 1.42 (0.69-2.92) and 2.91 (1.19-7.11) for glycated hemoglobin 5.7-<6.5% and ≥6.5%, respectively, compared with <5.7% (P trend = 0.011). Risk associations were stronger among individuals with a history of diabetes. We did not observe significant thresholds in the associations of glycated hemoglobin with kidney disease risk or retinopathy.

Conclusions: These data from a community-based, biracial population support the use of new 2010 American Diabetes Association glycated hemoglobin cut points for the diagnosis of diabetes.

FIG. 1.

Prevalence of any retinopathy by glycated hemoglobin category and history of diagnosed diabetes.

FIG. 2.

Adjusted HR of incident chronic kidney disease according to baseline glycated hemoglobin value. The figures show adjusted HRs from restricted cubic spline models. The shaded area is the 95% CI. The models are centered at the median (5.5%, 5.4%, and 7.4% in the total population, nondiabetic, and diabetic participants, respectively) and truncated at the 2.5th and the 97.5th percentiles of glycated hemoglobin in each population. The HRs were adjusted for age, sex, and race (black or white), low-density and high-density cholesterol levels, log transformed triglyceride level, BMI, waist-to-hip ratio, hypertension (yes or no), family history of diabetes (yes or no), education (less than high school, high school or equivalent, or college or above), alcohol use (currently, formerly, or never), physical activity index score, and smoking status (current smoker, former smoker, or never smoked). The model in A is further adjusted for diabetes medication use. The data are shown on a natural-log scale. (A high-quality color representation of this figure is available in the online issue.)

FIG. 3.

Adjusted OR of prevalent moderate/severe retinopathy* (ETDRS ≥35) according to baseline glycated hemoglobin value. The figures show adjusted ORs from restricted cubic spline models. The shaded area is the 95% CI. The models are centered at the median (5.5%, 5.4%, and 7.4% in the total population, nondiabetic, and diabetic participants, respectively) and truncated at the 2.5th and the 97.5th percentiles of glycated hemoglobin. The ORs were adjusted for age, sex, and race (black or white), low-density and high-density cholesterol levels, log-transformed triglyceride level, BMI, waist-to-hip ratio, hypertension (yes or no), family history of diabetes (yes or no), education (less than high school, high school or equivalent, or college or above), alcohol use (currently, formerly, or never), physical activity index score, and smoking status (current smoker, former smoker, or never smoked). The model in panel A is further adjusted for diabetes medication use. The data are shown on a natural-log scale. *Retinopathy was assessed at visit 3 in 1993–1995 (∼3 years after baseline). (A high-quality color representation of this figure is available in the online issue.)