Advertisement

Low serum creatinine to cystatin C ratio is independently associated with sarcopenia and high carotid plaque score in patients with type 2 diabetes

  • Author Footnotes
    1 Department of Internal Medicine, Yonsei University, Wonju College of Medicine, 20 Ilsan-ro, Wonju-si, Gangwon-do, 24642, Republic of Korea.
    Jang Yel Shin
    Footnotes
    1 Department of Internal Medicine, Yonsei University, Wonju College of Medicine, 20 Ilsan-ro, Wonju-si, Gangwon-do, 24642, Republic of Korea.
    Affiliations
    Department of Internal Medicine, Yonsei University, Wonju College of Medicine, Wonju, Republic of Korea
    Search for articles by this author
  • Author Footnotes
    1 Department of Internal Medicine, Yonsei University, Wonju College of Medicine, 20 Ilsan-ro, Wonju-si, Gangwon-do, 24642, Republic of Korea.
Published:February 11, 2022DOI:https://doi.org/10.1016/j.numecd.2022.02.005

      Highlights

      • CCR was positively correlated with appendicular skeletal muscle (ASM)/ body mass index (BMI) and grip strength (GS) in both genders.
      • Low CCR was independently associated with high carotid plaque score, especially after adjusting for ASM/ BMI and GS.

      Abstract

      Background and aims

      Low serum creatinine (Cr) to cystatin C (cysC) ratio has been suggested to be associated with low muscle mass and strength and poor prognosis in various chronic disease. We investigated the associations of CCR with sarcopenia and carotid plaque score (PS) in patients with type 2 diabetes mellitus.

      Methods and results

      A total of 1577 patients with type 2 diabetes were enrolled. High PS was defined as PS ≥ 3. Sarcopenia was assessed by the measurement of appendicular skeletal muscle mass (ASM) and grip strength (GS). Compared to the highest CCR group, the lowest tertile group was older; had higher C-reactive protein levels, CIMT, and PS, but lower cysC-based estimated glomerular filtration rate (cysC-eGFR), ASM/BMI, and GS. Positive correlations between CCR and ASM/BMI (r = 0.239 in men and 0.303 in women, p < 0.001) and GS (r = 0.282 in men and 0.270 in women, p < 0.001) were observed in both genders. Odds ratios and 95% confidence intervals for high PS after adjusting for age and sex were 1.22 (0.92–1.61, p = 0.18) in the middle and 1.74 (1.31–2.30, p < 0.001) in the lowest tertiles, respectively, with those of the lowest tertile remaining significant after further adjusting for multiple confounders.

      Conclusions

      Low CCR was independently associated with sarcopenia and high PS in patients with type 2 diabetes mellitus, especially after adjusting for ASM/BMI and GS.

      Keywords

      Abbreviations:

      ASM (appendicular skeletal muscle mass), BMI (body mass index), CCA (common carotid artery), CI (confidence interval), CIMT (carotid intima media thickness), CKD (chronic kidney disease), Cr (creatinine), cysC (cystatin C), CCR (Cr to cysC ratio), CVD (cardiovascular disease), DBP (diastolic blood pressure), eGFR (estimated glomerular filtration rate), FBG (fasting blood glucose), GS (grip strength), HbA1c (glycated hemoglobin), HDL (high-density lipoprotein), HOMA-IR (homeostasis model assessment–insulin resistance), hs-CRP (high-sensitive C-reactive protein), ICU (intensive care unit), OR (odds ratio), PS (plaque score), SBP (systolic blood pressure), TG (triglyceride), WC (waist circumference)
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Nutrition, Metabolism and Cardiovascular Diseases
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Pacifico J.
        • Geerlings M.A.J.
        • Reijnierse E.M.
        • Phassouliotis C.
        • Lim W.K.
        • Maier A.B.
        Prevalence of sarcopenia as a comorbid disease: a systematic review and meta-analysis.
        Exp Gerontol. 2020; 131: 110801
        • Chin S.O.
        • Rhee S.Y.
        • Chon S.
        • Hwang Y.C.
        • Jeong I.K.
        • Oh S.
        • et al.
        Sarcopenia is independently associated with cardiovascular disease in older Korean adults: the Korea National Health and Nutrition Examination Survey (KNHANES) from 2009.
        PLoS One. 2013; 8e60119
        • Park S.
        • Ham J.O.
        • Lee B.K.
        A positive association between stroke risk and sarcopenia in men aged >/= 50 years, but not women: results from the Korean National Health and Nutrition Examination Survey 2008-2010.
        J Nutr Health Aging. 2014; 18: 806-812
        • Liu H.M.
        • Zhang Q.
        • Shen W.D.
        • Li B.Y.
        • Lv W.Q.
        • Xiao H.M.
        • et al.
        Sarcopenia-related traits and coronary artery disease: a bi-directional Mendelian randomization study.
        Aging (Albany NY). 2020; 12: 3340-3353
        • Xia M.F.
        • Chen L.Y.
        • Wu L.
        • Ma H.
        • Li X.M.
        • Li Q.
        • et al.
        Sarcopenia, sarcopenic overweight/obesity and risk of cardiovascular disease and cardiac arrhythmia: a cross-sectional study.
        Clin Nutr. 2021; 40: 571-580
        • Butani L.
        • Polinsky M.S.
        • Kaiser B.A.
        • Baluarte H.J.
        Dietary protein intake significantly affects the serum creatinine concentration.
        Kidney Int. 2002; 61: 1907
        • Baxmann A.C.
        • Ahmed M.S.
        • Marques N.C.
        • Menon V.B.
        • Pereira A.B.
        • Kirsztajn G.M.
        • et al.
        Influence of muscle mass and physical activity on serum and urinary creatinine and serum cystatin C.
        Clin J Am Soc Nephrol. 2008; 3: 348-354
        • Yildiz A.
        • Tufan F.
        Lower creatinine as a marker of malnutrition and lower muscle mass in hemodialysis patients.
        Clin Interv Aging. 2015; 10: 1593
        • Patel S.S.
        • Molnar M.Z.
        • Tayek J.A.
        • Ix J.H.
        • Noori N.
        • Benner D.
        • et al.
        Serum creatinine as a marker of muscle mass in chronic kidney disease: results of a cross-sectional study and review of literature.
        J Cachexia Sarcopenia Muscle. 2013; 4: 19-29
        • Kashani K.B.
        • Frazee E.N.
        • Kukralova L.
        • Sarvottam K.
        • Herasevich V.
        • Young P.M.
        • et al.
        Evaluating muscle mass by using markers of kidney function: development of the sarcopenia index.
        Crit Care Med. 2017; 45: e23-e29
        • Osaka T.
        • Hamaguchi M.
        • Hashimoto Y.
        • Ushigome E.
        • Tanaka M.
        • Yamazaki M.
        • et al.
        Decreased the creatinine to cystatin C ratio is a surrogate marker of sarcopenia in patients with type 2 diabetes.
        Diabetes Res Clin Pract. 2018; 139: 52-58
        • Lin Y.L.
        • Chen S.Y.
        • Lai Y.H.
        • Wang C.H.
        • Kuo C.H.
        • Liou H.H.
        • et al.
        Serum creatinine to cystatin C ratio predicts skeletal muscle mass and strength in patients with non-dialysis chronic kidney disease.
        Clin Nutr. 2020; 39: 2435-2441
        • Tabara Y.
        • Kohara K.
        • Okada Y.
        • Ohyagi Y.
        • Igase M.
        Creatinine-to-cystatin C ratio as a marker of skeletal muscle mass in older adults: J-SHIPP study.
        Clin Nutr. 2020; 39: 1857-1862
        • Fu X.
        • Tian Z.
        • Wen S.
        • Sun H.
        • Thapa S.
        • Xiong H.
        • et al.
        A new index based on serum creatinine and cystatin C is useful for assessing sarcopenia in patients with advanced cancer.
        Nutrition. 2021; 82: 111032
        • Hirai K.
        • Tanaka A.
        • Homma T.
        • Goto Y.
        • Akimoto K.
        • Uno T.
        • et al.
        Serum creatinine/cystatin C ratio as a surrogate marker for sarcopenia in patients with chronic obstructive pulmonary disease.
        Clin Nutr. 2021; 40: 1274-1280
        • Jung C.Y.
        • Joo Y.S.
        • Kim H.W.
        • Han S.H.
        • Yoo T.H.
        • Kang S.W.
        • et al.
        Creatinine-cystatin C ratio and mortality in patients receiving intensive care and continuous kidney replacement therapy: a retrospective cohort study.
        Am J Kidney Dis. 2021; 77 (e1): 509-516
        • Lee H.S.
        • Park K.W.
        • Kang J.
        • Ki Y.J.
        • Chang M.
        • Han J.K.
        • et al.
        Sarcopenia index as a predictor of clinical outcomes in older patients with coronary artery disease.
        J Clin Med. 2020; 9
        • Lu Y.W.
        • Tsai Y.L.
        • Chou R.H.
        • Kuo C.S.
        • Chang C.C.
        • Huang P.H.
        • et al.
        Serum creatinine to cystatin C ratio is associated with major adverse cardiovascular events in patients with obstructive coronary artery disease.
        Nutr Metabol Cardiovasc Dis. 2021; 31: 1509-1515
        • Lorenz M.W.
        • Markus H.S.
        • Bots M.L.
        • Rosvall M.
        • Sitzer M.
        Prediction of clinical cardiovascular events with carotid intima-media thickness: a systematic review and meta-analysis.
        Circulation. 2007; 115: 459-467
        • Den Ruijter H.M.
        • Peters S.A.
        • Anderson T.J.
        • Britton A.R.
        • Dekker J.M.
        • Eijkemans M.J.
        • et al.
        Common carotid intima-media thickness measurements in cardiovascular risk prediction: a meta-analysis.
        JAMA. 2012; 308: 796-803
        • Willeit P.
        • Tschiderer L.
        • Allara E.
        • Reuber K.
        • Seekircher L.
        • Gao L.
        • et al.
        Carotid intima-media thickness progression as surrogate marker for cardiovascular risk: meta-analysis of 119 clinical trials involving 100 667 patients.
        Circulation. 2020; 142: 621-642
        • Spence J.D.
        IMT is not atherosclerosis.
        Atherosclerosis. 2020; 312: 117-118
        • Raggi P.
        • Stein J.H.
        Carotid intima-media thickness should not be referred to as subclinical atherosclerosis: a recommended update to the editorial policy at Atherosclerosis.
        Atherosclerosis. 2020; 312: 119-120
        • Nelson M.E.
        • Rejeski W.J.
        • Blair S.N.
        • Duncan P.W.
        • Judge J.O.
        • King A.C.
        • et al.
        Physical activity and public health in older adults: recommendation from the American College of Sports Medicine and the American Heart Association.
        Circulation. 2007; 116: 1094-1105
        • Chi X.H.
        • Li G.P.
        • Wang Q.S.
        • Qi Y.S.
        • Huang K.
        • Zhang Q.
        • et al.
        CKD-EPI creatinine-cystatin C glomerular filtration rate estimation equation seems more suitable for Chinese patients with chronic kidney disease than other equations.
        BMC Nephrol. 2017; 18: 226
        • Gepner A.D.
        • Young R.
        • Delaney J.A.
        • Budoff M.J.
        • Polak J.F.
        • Blaha M.J.
        • et al.
        Comparison of carotid plaque score and coronary artery calcium score for predicting cardiovascular disease events: the multi-ethnic study of atherosclerosis.
        J Am Heart Assoc. 2017; 6
        • Studenski S.A.
        • Peters K.W.
        • Alley D.E.
        • Cawthon P.M.
        • McLean R.R.
        • Harris T.B.
        • et al.
        The FNIH sarcopenia project: rationale, study description, conference recommendations, and final estimates.
        J Gerontol A Biol Sci Med Sci. 2014; 69: 547-558
        • Kizilarslanoglu M.C.
        • Kuyumcu M.E.
        • Yesil Y.
        • Halil M.
        Sarcopenia in critically ill patients.
        J Anesth. 2016; 30: 884-890
        • Peterson S.J.
        • Braunschweig C.A.
        Prevalence of sarcopenia and associated outcomes in the clinical setting.
        Nutr Clin Pract. 2016; 31: 40-48
        • Heo J.E.
        • Kim H.C.
        • Shim J.S.
        • Song B.M.
        • Bae H.Y.
        • Lee H.J.
        • et al.
        Association of appendicular skeletal muscle mass with carotid intima-media thickness according to body mass index in Korean adults.
        Epidemiol Health. 2018; 40e2018049
        • Seo D.H.
        • Lee Y.H.
        • Suh Y.J.
        • Ahn S.H.
        • Hong S.
        • Choi Y.J.
        • et al.
        Low muscle mass is associated with carotid atherosclerosis in patients with type 2 diabetes.
        Atherosclerosis. 2020; 305: 19-25
        • Campos A.M.
        • Moura F.A.
        • Santos S.N.
        • Freitas W.M.
        • Sposito A.C.
        • Brasilia Study on Healthy A.
        • et al.
        Sarcopenia, but not excess weight or increased caloric intake, is associated with coronary subclinical atherosclerosis in the very elderly.
        Atherosclerosis. 2017; 258: 138-144
        • Moorthi R.N.
        • Avin K.G.
        Clinical relevance of sarcopenia in chronic kidney disease.
        Curr Opin Nephrol Hypertens. 2017; 26: 219-228
        • Bataille S.
        • Chauveau P.
        • Fouque D.
        • Aparicio M.
        • Koppe L.
        Myostatin and muscle atrophy during chronic kidney disease.
        Nephrol Dial Transplant. 2021; 36: 1986-1993https://doi.org/10.1093/ndt/gfaa129
        • Yilmaz M.I.
        • Sonmez A.
        • Saglam M.
        • Yaman H.
        • Cayci T.
        • Kilic S.
        • et al.
        Reduced proteinuria using ramipril in diabetic CKD stage 1 decreases circulating cell death receptor activators concurrently with ADMA. A novel pathophysiological pathway?.
        Nephrol Dial Transplant. 2010; 25: 3250-3256
        • Verzola D.
        • Milanesi S.
        • Bertolotto M.
        • Garibaldi S.
        • Villaggio B.
        • Brunelli C.
        • et al.
        Myostatin mediates abdominal aortic atherosclerosis progression by inducing vascular smooth muscle cell dysfunction and monocyte recruitment.
        Sci Rep. 2017; 7: 46362
        • Gansevoort R.T.
        • Correa-Rotter R.
        • Hemmelgarn B.R.
        • Jafar T.H.
        • Heerspink H.J.
        • Mann J.F.
        • et al.
        Chronic kidney disease and cardiovascular risk: epidemiology, mechanisms, and prevention.
        Lancet. 2013; 382: 339-352
        • Parikh N.I.
        • Hwang S.J.
        • Larson M.G.
        • Meigs J.B.
        • Levy D.
        • Fox C.S.
        Cardiovascular disease risk factors in chronic kidney disease: overall burden and rates of treatment and control.
        Arch Intern Med. 2006; 166: 1884-1891
        • Harada K.
        • Suzuki S.
        • Ishii H.
        • Aoki T.
        • Hirayama K.
        • Shibata Y.
        • et al.
        Impact of skeletal muscle mass on long-term adverse cardiovascular outcomes in patients with chronic kidney disease.
        Am J Cardiol. 2017; 119: 1275-1280
        • Hanatani S.
        • Izumiya Y.
        • Onoue Y.
        • Tanaka T.
        • Yamamoto M.
        • Ishida T.
        • et al.
        Non-invasive testing for sarcopenia predicts future cardiovascular events in patients with chronic kidney disease.
        Int J Cardiol. 2018; 268: 216-221
        • Morioka T.
        Myostatin: the missing link between sarcopenia and cardiovascular disease in chronic kidney disease?.
        J Atherosclerosis Thromb. 2020; 27: 1036-1038