Introduction
Prediabetes is a transitional stage from normal glucose tolerance (NGT) to overt diabetes.1 Chinese adults have been reported to have an overall high prevalence of prediabetes of 35.7%.2 It has been well established that individuals with prediabetes are at high risk of progressing to diabetes,3 and its consequent increased risk of long-term complications in the eye, kidney and cardiovascular system.4–6 We here focused our work on the relationship of prediabetes to chronic kidney disease (CKD) in the Chinese adult population.
Studies have found that a large number of patients with diabetes had an estimated glomerular filtration rate (eGFR) <60 mL/min per 1.73 m2 but without microalbuminuria, and even more in the general population.7–9 In addition, it has been reported that the proportion of individuals with eGFR <60 mL/min per 1.73 m2 was obviously higher than those with elevated urine albumin in the Chinese population over 60 years old (90.6% vs 19.8%).10 Glomerular hyperfiltration, an early manifestation of diabetic kidney disease, has been confirmed to predict an elevated urinary albumin and decreased eGFR in patients with diabetes.11 Therefore, in this study, we focused on the value of eGFR, including its elevation and decline, and used decreased eGFR to define CKD. Although it is well established that diabetes increases the risk of CKD,12 13 whether prediabetes is also a risk factor for impairment of kidney function and occurrence of CKD are unclear. The data from the Framingham Heart Study offspring cohort obtained between 1991 and 1995 suggested that it may not be prediabetes but rather cardiovascular disease risk factors, including gender, age, blood pressure and plasma lipids that are more predictive of the occurrence of CKD.14 Contrary to this report, a cross-sectional study from the Cooperative Health Research in the Augsburg Region (KORA) instead suggested that prediabetes might have harmful effects on the kidney.15 There have also been conflicting reports regarding the association between prediabetes and CKD in the Chinese population.16 17 Fasting plasma glucose (FPG) and 2-hour plasma glucose (2hPG) have been commonly used for the diagnosis of diabetes; and recently, glycated hemoglobin A1c (HbA1c), a measure of long term glucose homeostasis, has also been recommended for diagnosis of diabetes. The KORA study suggested that FPG, 2hPG and HbA1c were all associated with CKD15; however, studies from China, Japan and Korea indicated that it was elevated HbA1c or impaired glucose tolerance (IGT), but not impaired fasting glucose (IFG) increased the risk for CKD,18–20 and one study based on the Systolic Blood Pressure Intervention Trial concluded that FPG was not associated with the development of CKD.21 Therefore, which of these prediabetic glycemic indices is/are genuinely associated with the occurrence of CKD remain unclear.
It is generally accepted that the occurrence of diabetes and its complications in high-risk individuals can be prevented or at least alleviated by lifestyle modification and pharmacological intervention.22 Therefore, it behooves us to determine whether prediabetes is associated with occurrence of CKD and identify the best measurement(s) of glycemic levels that could predict an increased risk of CKD. In current clinical practice, there are no specific cut-off points for the above-mentioned glycemic indices (FPG, 2hPG, HbA1c) for the prediction of CKD. The postulated cut-off points in these three glycemic indices might well represent different phenotypes of prediabetes. In fact, the international standard for the diagnosis of prediabetes is not uniform. According to the WHO, the diagnosis of prediabetes is a FPG of between 6.1 and 6.9 mmol/L (110–125 mg/dL) or a 2hPG of between 7.8 and 11.0 mmol/L (140–199 mg/dL).23 However, according to the American Diabetes Association (ADA), prediabetes is diagnosed as a FPG between 5.6 and 6.9 mmol/L (100–125 mg/dL; “IFG”), or a 2hPG following a 75 g oral glucose tolerance test (OGTT) between 7.8–11.0 mmol/L (140–199 mg/dL; “IGT”) or a HbA1c between 39 and 46 mmol/mol (5.7%–6.4%).24 Which of these two criteria of prediabetes is more sensitive in identifying people in China to be considered at high risk is still unclear. Currently, China uses the WHO criteria for diagnosing prediabetes. Identifying the appropriate cut-off points for these glycemic indices in defining the relevant prediabetes phenotypes for China could provide valuable information in predicting and therefore preventing the occurrence of CKD.
The above provided the motivation for us to pursue the following aims. First, we examined the influence of prediabetes and its phenotypes on CKD occurrence in the Chinese population. Second, we identified the appropriate cut-off point for each of the three glycemic indices that could predict CKD occurrence, and compared the diagnostic value of these cut-off points with the criteria for prediabetes as defined by WHO and ADA.