Of the 4,924 people who participated at the baseline examination, 4,901 had information on diabetes status; 441 (9.0%) had diabetes and 92 (1.9%) were suspected of having diabetes. Of the remaining 4,368 subjects without diabetes, 896 (18.3%) were alive but not examined at the 5-year follow-up examination due to refusal or they were unable to be located. Incidence analyses in this report are limited to the remaining 3,472 people at risk of developing diabetes, including 714 people who died at any follow-up examination. Persons without diabetes incidence data were more likely to be older and, after adjusting for age, were more likely to be a current smoker and have a higher mean serum cystatin C than participants included in analyses.
The 15-year cumulative incidence of diabetes was estimated to be 9.6%. Characteristics of the study population by those who did and did not develop diabetes or died are presented in . While adjusting for age and sex, people with higher levels of serum cystatin C were more likely to die (p<0.05). Also, people who died had more frequent history of cardiovascular disease and gross proteinuria history (p<0.05). People who developed diabetes during the 15-year follow-up were older, had higher BMI, and were more likely to be male and a current smoker (p<0.05). Additionally, people who developed diabetes had higher mean glycosylated hemoglobin levels and mean systolic and diastolic BP at the baseline examination, but did not differ by mean serum total cholesterol levels from people who did not develop diabetes (p<0.05). Also, people who developed diabetes were more likely to be hypertensive, were more likely to have a history of cardiovascular disease and to use beta-blockers, diuretics and nonsteroidal anti-inflammatory drugs (NSAIDs) than people who did not develop diabetes. People who developed diabetes had higher serum cystatin C levels and lower cystatin C based GFR, but did not differ by serum creatinine and creatinine based GFR levels and gross proteinuria status from people who did not develop diabetes.
Baseline Characteristics by Diabetes Incidence or Death Status at the 1988–1990 Beaver Dam Eye Study Examination.
Our median value and interquartile range for cystatin C were 0.85 and 0.75–0.99, correspondingly. On the log scale it corresponded to median value of −0.16 and interquartile range of −0.29 to −0.01. The geometric mean of cystatin C was 0.83 for people who did not develop diabetes, 0.90 for those who developed diabetes and 1.03 for those who died.
The results of multivariate analysis showed that serum cystatin C at baseline was associated with diabetes development after adjustment for sex and age (). Further sequential adjustment for BMI, smoking status, glycosylated hemoglobin, hypertension history, gross proteinuria and chronic kidney disease status showed that serum cystatin C remained associated with the incidence of diabetes (OR per log of cystatin C 2.19; 95% CI 1.02, 4.68). It corresponded to OR 1.15; 95% CI 1.01; 1.31 per 50% increase of cystatin C. Serum cystatin C in our study was weakly correlated with markers of inflammation such as hsCRP (r=0.19, p=0.0001). Meanwhile, the association of serum cystatin C with the incidence of diabetes remained significant after further adjustment for serum C-reactive protein (OR 2.09; 95% CI 1.02, 4.11). Estimated GFR based on serum cystatin C levels was related to the incidence of diabetes after controlling for age and sex (OR ml min−1 1.73 m−2 0.98, 95% CI 0.97, 0.99, p<0.0001). In contrast, GFR based on serum creatinine using the MDRD equation was not related to the incidence of diabetes after controlling for age and sex (OR ml min−1 1.73 m−2 1.00, 95%CI 0.99, 1.01, p=0.94). Stratification by kidney disease status () showed that the association of serum cystatin C with the incidence of diabetes was similar in those people with and without CKD (). The association of serum cystatin C with the incidence of diabetes was significant after adjustment for age and sex in both groups. Body mass index was the strongest confounder of the association of cystatin C with incident diabetes in both groups. The association did not remain significant after adjustment for BMI in persons with kidney disease and after the adjustment for glycosylated hemoglobin in persons without kidney disease. After controlling for confounding factors, the odds of having incident diabetes was not different in both subgroups ().
Impact of Sequential Adjustment on Cystatin C Related Differences in 15-year Cumulative Diabetes Incidence in the Beaver Dam Eye Study.