Diabetes Metab J.  2022 May;46(3):476-485. 10.4093/dmj.2021.0074.

Normalized Creatinine-to-Cystatin C Ratio and Risk of Diabetes in Middle-Aged and Older Adults: The China Health and Retirement Longitudinal Study

• Qiu S
• Cai X
• Xie B
• Yuan Y
• Sun Z
• Wu T

• KMID: 2530186
• DOI: http://doi.org/10.4093/dmj.2021.0074

Abstract

Background
Creatinine-to-cystatin C ratio is recently suggested to be a surrogate marker for sarcopenia. However, little is known about its association with diabetes. This study aimed to fill in this gap based on a large-scale prospective cohort.
Methods
A population-based representative sample of 5,055 participants aged ≥45 years from the China Health and Retirement Longitudinal Study was enrolled between 2011 and 2012 and followed at least once during the subsequent surveys at 2013, 2015, or 2018. Creatinine-to-cystatin C ratio was calculated and normalized by body weight. Incident diabetes was ascertained by plasma glucose, glycosylated hemoglobin, self-reported history, or use of anti-diabetic drugs. Logistic regression analysis and mediation analysis were employed.
Results
During follow-up, 634 participants developed diabetes. The risk of diabetes was gradually and significantly decreased with increased normalized creatinine–cystatin C ratio. The multivariable-adjusted odds ratio for diabetes was 0.91 (95% confidence interval, 0.83 to 0.99) per 1 standard deviation higher of normalized creatinine-to-cystatin C ratio, and this relationship remained significant after controlling for muscle strength. The risk reduction in diabetes was significantly larger in participants with normal-weight and high normalized creatinine-to-cystatin C ratio compared with those with overweight/obesity and high normalized creatinine-to-cystatin C ratio (P_interaction=0.01). Insulin resistance and inflammation appeared to be key mediators accounting for the observed relationship between normalized creatinine-to-cystatin C ratio and risk of diabetes, with their mediating effect being 93.1% and 22.0%, respectively.
Conclusion
High normalized creatinine-to-cystatin C ratio is associated with reduced risk of diabetes in middle-aged and older adults.

Keyword

Creatinine; Cystatin C; Diabetes mellitus; Insulin resistance; Longitudinal studies; Muscle strength

Figure

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  Fig. 1. Cubic spline curve for the relationship between normalized creatinine-to-cystatin C ratio and risk of diabetes. The cubic spline curve analysis was adjusted for age, gender, history of smoking and drinking, presence of hypertension, dyslipidemia, and heart disease, mean arterial pressure, glycosylated hemoglobin, total cholesterol/high-density lipoprotein, triglyceride, low-density lipoprotein, uric acid, and high-sensitivity C-reactive protein. OR, odds ratio.

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  Fig. 2. Mediation analysis for the relationship between normalized creatinine-to-cystatin C ratio and risk of diabetes. Mediation analysis (which included the tests for coefficients of a, b, and c) was conducted based on the generalized structural equation model using “GSEM” command in Stata. SBP, systolic blood pressure; DBP, diastolic blood pressure; FPG, fasting plasma glucose; HbA1c, glycosylated hemoglobin; METS-IR, the metabolic score for insulin resistance; TC, total cholesterol; TG, triglyceride; HDL, high-density lipoprotein; LDL, low-density lipoprotein; hs-CRP, high-sensitivity C-reactive protein; eGFR, estimated glomerular filtration rate.

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