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Published in: BMC Geriatrics 1/2020

Open Access 01-12-2020 | Sarcopenia | Research article

Low serum albumin, aspartate aminotransferase, and body mass are risk factors for frailty in elderly people with diabetes–a cross-sectional study

Authors: Ikumi Yanagita, Yuya Fujihara, Chikayo Iwaya, Yuichi Kitajima, Misuzu Tajima, Masanao Honda, Yuji Teruya, Hideko Asakawa, Tomoko Ito, Terumi Eda, Noriko Yamaguchi, Yumi Kayashima, Mihoko Yoshimoto, Mayumi Harada, Shoji Yoshimoto, Eiji Aida, Toshihiko Yanase, Hajime Nawata, Kazuo Muta

Published in: BMC Geriatrics | Issue 1/2020

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Abstract

Background

Frailty is broadly characterized by vulnerability and decline in physical, mental and social activities and is more common in elderly patients with type 2 diabetes mellitus (T2DM). Frailty is closely associated with nutrition, muscle strength, inflammation, and hormones etc. In hormones, dehydroepiandrosterone sulfate (DHEA-S) and cortisol are suggested to be such candidates affecting frailty. Little investigation has been performed using a wider range of measures of frailty to clarify risk factors for frailty including the above two hormones.

Methods

We performed a cross-sectional study to investigate the risk factors for frailty in elderly T2DM patients (n = 148; ≥65 years), using a broad assessment, the clinical frailty scale. We compared parameters between the non-frail and frail groups using the unpaired t and Mann-Whitney U tests. The Jonckheere-Therpstra test was used to identify relationships with the severity of frailty, and risk factors were identified using binary regression analysis.

Results

Simple regression analysis identified a number of significant risk factors for frailty, including DHEAS < 70 μg/dL and cortisol/DHEA-S ratio ≥ 0.2. Multiple regression analysis showed that low albumin (< 4.0 g/dl) (odds ratio [OR] = 5.79, p < 0.001), low aspartate aminotransferase (AST) activity (< 25 IU/L) (OR = 4.34, p = 0.009), and low body mass (BM) (< 53 kg) (OR = 3.85, p = 0.012) were independent risk factors for frailty. A significant decrease in DHEA-S and a significant increase in the cortisol/DHEA-S ratio occurred alongside increases in the severity of frailty. DHEA-S concentration positively correlated with both serum albumin and BM.

Conclusions

Hypoalbuminemia, low AST, and low BM are independent risk factors for frailty in elderly T2DM patients, strongly implying relative malnutrition in these frail patients. DHEA-S may be important for the maintenance of liver function and BM. A decrease in DHEA-S and an increase in the cortisol/DHEAS ratio may be involved in the mechanism of the effect of malnutrition in elderly T2DM patients.
Literature
1.
go back to reference Woods NF, LaCroix AZ, Gray SL, Aragaki A, Cochrane BB, Brunner RL, et al. Frailty: emergence and consequences in women aged 65 and older in the Women’s health initiative observational study. J Am Geriatr Soc. 2005;53:1321–30.CrossRef Woods NF, LaCroix AZ, Gray SL, Aragaki A, Cochrane BB, Brunner RL, et al. Frailty: emergence and consequences in women aged 65 and older in the Women’s health initiative observational study. J Am Geriatr Soc. 2005;53:1321–30.CrossRef
2.
go back to reference Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, et al. Cardiovascular health study collaborative research group. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001;56:M146–56.CrossRef Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, et al. Cardiovascular health study collaborative research group. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001;56:M146–56.CrossRef
3.
go back to reference Rockwood K, Howlett SE, MacKnight C, Beattie BL, Bergman H. He bert R, et al. prevalence, attributes, and outcomes of fitness and frailty in community-dwelling older adults: report from the Canadian study of health and aging. J Geront A Biol Sci Med Sci. 2004;59(12):1310–7.CrossRef Rockwood K, Howlett SE, MacKnight C, Beattie BL, Bergman H. He bert R, et al. prevalence, attributes, and outcomes of fitness and frailty in community-dwelling older adults: report from the Canadian study of health and aging. J Geront A Biol Sci Med Sci. 2004;59(12):1310–7.CrossRef
4.
go back to reference Yanagita I, Fujihara Y, Eda T, Tajima M, Yonemura K, Kawajiri T, et al. Low glycated hemoglobin level is associated with severity of frailty in Japanese elderly diabetes patients. J Diabetes Investig. 2018;9(2):419–25.CrossRef Yanagita I, Fujihara Y, Eda T, Tajima M, Yonemura K, Kawajiri T, et al. Low glycated hemoglobin level is associated with severity of frailty in Japanese elderly diabetes patients. J Diabetes Investig. 2018;9(2):419–25.CrossRef
5.
go back to reference Yanase T, Yanagita I, Muta K, Nawata H. Frailty in elderly diabetes patients. Endocr J. 2018;65:1–11.CrossRef Yanase T, Yanagita I, Muta K, Nawata H. Frailty in elderly diabetes patients. Endocr J. 2018;65:1–11.CrossRef
6.
go back to reference Abdelhafiz AH, Loo BE, Hensey N, Bailey C, Sinclair A. The U -shaped relationship of traditional cardiovascular risk factors and adverse outcomes in later life. Aging Dis. 2012;3(6):454–64.PubMedPubMedCentral Abdelhafiz AH, Loo BE, Hensey N, Bailey C, Sinclair A. The U -shaped relationship of traditional cardiovascular risk factors and adverse outcomes in later life. Aging Dis. 2012;3(6):454–64.PubMedPubMedCentral
7.
go back to reference Abdelhafiz AH, Sinclair AJ. Low HbAlc and increased mortality risk-is frailty a confounding factor? Aging Dis. 2015;6(4):262–70.CrossRef Abdelhafiz AH, Sinclair AJ. Low HbAlc and increased mortality risk-is frailty a confounding factor? Aging Dis. 2015;6(4):262–70.CrossRef
8.
go back to reference Liguori I, Russo G, Aran L, Bulli G, Curcio F, Della-Morte D, et al. Sarcopenia: assessment of disease burden and strategies to improve outcomes. Clin Interv Aging. 2018;13:913–27.CrossRef Liguori I, Russo G, Aran L, Bulli G, Curcio F, Della-Morte D, et al. Sarcopenia: assessment of disease burden and strategies to improve outcomes. Clin Interv Aging. 2018;13:913–27.CrossRef
9.
go back to reference Yanagita I, Fujihara Y, Kitajima Y, Tajima M, Honda M, Kawajiri T, et al. A high serum cortisol/DHEA-S ratio is a risk factor for sarcopenia in elderly diabetic patients. J Endocrine Soc. 2019;3(4):801–13.CrossRef Yanagita I, Fujihara Y, Kitajima Y, Tajima M, Honda M, Kawajiri T, et al. A high serum cortisol/DHEA-S ratio is a risk factor for sarcopenia in elderly diabetic patients. J Endocrine Soc. 2019;3(4):801–13.CrossRef
10.
go back to reference Orentreich N, Brind JL, Rizer RL, Vogelman JH. Age changes and sex differences in serum dehydroepiandrosterone sulfate concentration throughout adulthood. J Clin Endocrinol Metab. 1984;59:551–5.CrossRef Orentreich N, Brind JL, Rizer RL, Vogelman JH. Age changes and sex differences in serum dehydroepiandrosterone sulfate concentration throughout adulthood. J Clin Endocrinol Metab. 1984;59:551–5.CrossRef
11.
go back to reference Nawata H, Yanase T, Goto K, Okabe T, Ashida K. Mechanism of action of anti-aging DHEA-S and the replacement of DHEA-S. Mech Aging Dis. 2002;123:1101–6.CrossRef Nawata H, Yanase T, Goto K, Okabe T, Ashida K. Mechanism of action of anti-aging DHEA-S and the replacement of DHEA-S. Mech Aging Dis. 2002;123:1101–6.CrossRef
12.
go back to reference Leng SX, Cappola AR, Andersen RE, Blackman MR, Koenig K, Blair M, et al. Serum levels of insulin-like growth factor-l (IGF-1) and dehydroepiandrosterone sulfate (DHEA-S), and their relationships with serum interleukin-6, in the geriatric syndrome of frailty. Aging Clin Exp Res. 2004;16(2):153–7.CrossRef Leng SX, Cappola AR, Andersen RE, Blackman MR, Koenig K, Blair M, et al. Serum levels of insulin-like growth factor-l (IGF-1) and dehydroepiandrosterone sulfate (DHEA-S), and their relationships with serum interleukin-6, in the geriatric syndrome of frailty. Aging Clin Exp Res. 2004;16(2):153–7.CrossRef
13.
go back to reference Voznesensky M, Walsh A, Dauser D, Brindisi J, Kenny AM. The relationship between dehydroepiandrosterone and frailty in older men and women. Age Ageing. 2009;38(4):401–6.CrossRef Voznesensky M, Walsh A, Dauser D, Brindisi J, Kenny AM. The relationship between dehydroepiandrosterone and frailty in older men and women. Age Ageing. 2009;38(4):401–6.CrossRef
14.
go back to reference Baylis D, Bartlett DB, Syddall HE, Ntani G, Gale CR, Cooper C, et al. Immune-endocrine biomarkers as predictors of frailty and mortality: a 10-year longitudinal study in community-dwelling older people. Age. 2013;35:963–71.CrossRef Baylis D, Bartlett DB, Syddall HE, Ntani G, Gale CR, Cooper C, et al. Immune-endocrine biomarkers as predictors of frailty and mortality: a 10-year longitudinal study in community-dwelling older people. Age. 2013;35:963–71.CrossRef
15.
go back to reference Swiecicka A, Lunt M, Ahern T, O’Neill TW, Bartfai G, Casanueva FF, et al. Nonandrogenic anabolic hormones predict risk of frailty: European male ageing study prospective data. J Clin Endocrinol Metab. 2017;102(8):2799–806.CrossRef Swiecicka A, Lunt M, Ahern T, O’Neill TW, Bartfai G, Casanueva FF, et al. Nonandrogenic anabolic hormones predict risk of frailty: European male ageing study prospective data. J Clin Endocrinol Metab. 2017;102(8):2799–806.CrossRef
16.
go back to reference Forti P, Maltoni B, Olivelli V, Pirazzoli GL, Ravaglia G, Zoli M. Serum dehydroepiandrosterone sulfate and adverse health outcomes in older men and women. Rejuvenation Res. 2012;15(4):349–58.CrossRef Forti P, Maltoni B, Olivelli V, Pirazzoli GL, Ravaglia G, Zoli M. Serum dehydroepiandrosterone sulfate and adverse health outcomes in older men and women. Rejuvenation Res. 2012;15(4):349–58.CrossRef
17.
go back to reference Seino Y, Nanjo K, Tajima N, Kadowaki T, Kashiwagi A, Araki E, et al. Committee of the Japan Diabetes Society on the diagnostic criteria of diabetes mellitus: report of the committee on the classification and diagnostic criteria of diabetes mellitus. J Diabetes Investig. 2010;1(5):212–28.CrossRef Seino Y, Nanjo K, Tajima N, Kadowaki T, Kashiwagi A, Araki E, et al. Committee of the Japan Diabetes Society on the diagnostic criteria of diabetes mellitus: report of the committee on the classification and diagnostic criteria of diabetes mellitus. J Diabetes Investig. 2010;1(5):212–28.CrossRef
20.
go back to reference Cruz-Jentoft AJ, Baeyens JP, Bauer JM, Boirie Y, Cederholm T, Landi F, et al. European working group on sarcopenia in older people. Sarcopenia: European consensus on definition and diagnosis: report of the European working group on sarcopenia in older people. Age Ageing. 2010;39(4):412–23.CrossRef Cruz-Jentoft AJ, Baeyens JP, Bauer JM, Boirie Y, Cederholm T, Landi F, et al. European working group on sarcopenia in older people. Sarcopenia: European consensus on definition and diagnosis: report of the European working group on sarcopenia in older people. Age Ageing. 2010;39(4):412–23.CrossRef
21.
go back to reference Chen LK, Liu LK, Woo J, Assantachai P, Auyeung TW, Bahyah KS, et al. Sarcopenia in Asia: consensus report of the Asian working Group for Sarcopenia. J Am Med Dir Assoc. 2014;15(2):95–101.CrossRef Chen LK, Liu LK, Woo J, Assantachai P, Auyeung TW, Bahyah KS, et al. Sarcopenia in Asia: consensus report of the Asian working Group for Sarcopenia. J Am Med Dir Assoc. 2014;15(2):95–101.CrossRef
23.
go back to reference Le Couteur DG, Blyth FM, Creasey HM, Handelsman DJ, Naganathan V, Sambrook PN, et al. The association of alanine transaminase with aging, frailty, and mortality. J Gerontol A Biol Sci Med Sci. 2010;65(7):712–7.CrossRef Le Couteur DG, Blyth FM, Creasey HM, Handelsman DJ, Naganathan V, Sambrook PN, et al. The association of alanine transaminase with aging, frailty, and mortality. J Gerontol A Biol Sci Med Sci. 2010;65(7):712–7.CrossRef
24.
go back to reference Vespasiani-Gentilucci U, De Vincentis A, Ferrucci L, Bandinelli S, Antonelli Incalzi R, Picardi A. Low alanine aminotransferase levels in the elderly population: frailty, disability, sarcopenia and reduced survival. J Gerontol A Biol Med Sci. 2018;73(7):925–30.CrossRef Vespasiani-Gentilucci U, De Vincentis A, Ferrucci L, Bandinelli S, Antonelli Incalzi R, Picardi A. Low alanine aminotransferase levels in the elderly population: frailty, disability, sarcopenia and reduced survival. J Gerontol A Biol Med Sci. 2018;73(7):925–30.CrossRef
25.
go back to reference Elinav E, Ackerman Z, Maaravi Y, Ben-Dov IZ, Ein-Mor E, Stessman J. Low alanine aminotransferase activity in older people is associate with greater long-term mortality. J Am Geriatr Soc. 2006;54(11):1719–24.CrossRef Elinav E, Ackerman Z, Maaravi Y, Ben-Dov IZ, Ein-Mor E, Stessman J. Low alanine aminotransferase activity in older people is associate with greater long-term mortality. J Am Geriatr Soc. 2006;54(11):1719–24.CrossRef
26.
go back to reference Vanderlinde RE. Review of pyridoxal phosphate and the transaminases in liver disease. Ann Clin Lab Sci. 1986;16(2):79–93.PubMed Vanderlinde RE. Review of pyridoxal phosphate and the transaminases in liver disease. Ann Clin Lab Sci. 1986;16(2):79–93.PubMed
28.
go back to reference Fukui M, Ose H, Nakayama I, Hosoda H, Asano M, Kadono M, et al. Association between urinary albumin excretion and serum dehydroepiandrosterone sulfate concentrations in women with type 2 diabetes. Diabetes Care. 2007;30(7):1886–8.CrossRef Fukui M, Ose H, Nakayama I, Hosoda H, Asano M, Kadono M, et al. Association between urinary albumin excretion and serum dehydroepiandrosterone sulfate concentrations in women with type 2 diabetes. Diabetes Care. 2007;30(7):1886–8.CrossRef
29.
go back to reference Charlton M, Angulo P, Chalasani N, Merriman R, Viker K, Charatcharoenwitthaya P, et al. Low circulating levels of dehydroepiandrosterone in histologically advanced nonalcoholic fatty liver disease. Hepatology. 2008;47:484–92.CrossRef Charlton M, Angulo P, Chalasani N, Merriman R, Viker K, Charatcharoenwitthaya P, et al. Low circulating levels of dehydroepiandrosterone in histologically advanced nonalcoholic fatty liver disease. Hepatology. 2008;47:484–92.CrossRef
30.
go back to reference Sumida Y, Naitoa Y, Hashimoto E, Aoi W, Takahashi Y, Yonei Y, et al. Science of nonalcoholic fatty liver disease in anti-aging medicine 2011. Anti-aging Medicine. 2012;9:24–33.CrossRef Sumida Y, Naitoa Y, Hashimoto E, Aoi W, Takahashi Y, Yonei Y, et al. Science of nonalcoholic fatty liver disease in anti-aging medicine 2011. Anti-aging Medicine. 2012;9:24–33.CrossRef
31.
go back to reference Hakkak R, Bell A, Korourian S. Dehydroepiandrosterone (DHEA) feeding protects liver steatosis in obese breast cancer rat model. Sci Pharm. 2017;85:13–22.CrossRef Hakkak R, Bell A, Korourian S. Dehydroepiandrosterone (DHEA) feeding protects liver steatosis in obese breast cancer rat model. Sci Pharm. 2017;85:13–22.CrossRef
32.
go back to reference Teng Y, Radde BN, Litchfield LM, Ivanova MM, Prough RA, Clark BJ, et al. Dehydroepiandrosterone activation of G-protein-coupled estrogen receptor rapidly stimulate microRNA-21 transcription in human hepatocellular carcinoma cells. J Biol Chem. 2015;290:15799–811.CrossRef Teng Y, Radde BN, Litchfield LM, Ivanova MM, Prough RA, Clark BJ, et al. Dehydroepiandrosterone activation of G-protein-coupled estrogen receptor rapidly stimulate microRNA-21 transcription in human hepatocellular carcinoma cells. J Biol Chem. 2015;290:15799–811.CrossRef
33.
go back to reference Ong KK. Potau N, Petry CJ, Jones R, ness AR, honour JW, et al. opposing influence of prenatal and postnatal weight gain on adrenarche in normal boys and girls. J Clin Endocrinol Metab. 2004;89:2647–51.CrossRef Ong KK. Potau N, Petry CJ, Jones R, ness AR, honour JW, et al. opposing influence of prenatal and postnatal weight gain on adrenarche in normal boys and girls. J Clin Endocrinol Metab. 2004;89:2647–51.CrossRef
34.
go back to reference Corvalan C, Uauy R, Mericq V. Obesity is positively associated with dehydroepiandrosterone sulfate concentrations at 7 y in Chilean children of normal birth weight. Am J Clin Nutr. 2013;97:318–25.CrossRef Corvalan C, Uauy R, Mericq V. Obesity is positively associated with dehydroepiandrosterone sulfate concentrations at 7 y in Chilean children of normal birth weight. Am J Clin Nutr. 2013;97:318–25.CrossRef
36.
go back to reference Taniguchi S, Yanase T, Haji M, Ishibashi K, Takayanagi R, Nawata H. The antiobesity of dehydroepiandrosterone in castrated or noncastrated obese Zucker male rats. Obes Res. 1995;1(Suppl 5):639–43.CrossRef Taniguchi S, Yanase T, Haji M, Ishibashi K, Takayanagi R, Nawata H. The antiobesity of dehydroepiandrosterone in castrated or noncastrated obese Zucker male rats. Obes Res. 1995;1(Suppl 5):639–43.CrossRef
37.
go back to reference Villareal DT, Holloszy JO, et al. Effect of DHEA on abdominal fat and insulin action in elderly women and men: a randomized controlled trial. JAMA. 2004;292:2243–8.CrossRef Villareal DT, Holloszy JO, et al. Effect of DHEA on abdominal fat and insulin action in elderly women and men: a randomized controlled trial. JAMA. 2004;292:2243–8.CrossRef
38.
go back to reference McNelis JC, Manolopoulos KN, Gathercole LL, Bujalska IJ, Stewart PM, Tomlinson JW, et al. Dehydroepiandrosterone exerts antiglucocorticoid action on human preadipocyte proliferation, differentiation, and glucose uptake. Am J Physiol Endocrinol Metab. 2013;305(9):E1134–44.CrossRef McNelis JC, Manolopoulos KN, Gathercole LL, Bujalska IJ, Stewart PM, Tomlinson JW, et al. Dehydroepiandrosterone exerts antiglucocorticoid action on human preadipocyte proliferation, differentiation, and glucose uptake. Am J Physiol Endocrinol Metab. 2013;305(9):E1134–44.CrossRef
39.
go back to reference Ashida K, Goto K, Zhao Y, Okabe T, Yanase T, Takayanagi R, et al. Dehydroepiandrosterone negatively regulates the p38 mitogen-activated protein kinase pathway by a novel mitogen-activated protein kinase phosphatase. Biochim Biophys Acta. 2005;1728(1–2):84–94.CrossRef Ashida K, Goto K, Zhao Y, Okabe T, Yanase T, Takayanagi R, et al. Dehydroepiandrosterone negatively regulates the p38 mitogen-activated protein kinase pathway by a novel mitogen-activated protein kinase phosphatase. Biochim Biophys Acta. 2005;1728(1–2):84–94.CrossRef
40.
go back to reference Watanabe T, Ashida K, Goto K, Nawata H, Takayanagi R, Yanase T, et al. Dehydroepiandrosterone-enhanced dual specificity protein phosphatase (DDSP) prevents diet -induced and genetic obesity. Biochem Biophys Res Commun. 2015;468(1–2):196–201.CrossRef Watanabe T, Ashida K, Goto K, Nawata H, Takayanagi R, Yanase T, et al. Dehydroepiandrosterone-enhanced dual specificity protein phosphatase (DDSP) prevents diet -induced and genetic obesity. Biochem Biophys Res Commun. 2015;468(1–2):196–201.CrossRef
Metadata
Title
Low serum albumin, aspartate aminotransferase, and body mass are risk factors for frailty in elderly people with diabetes–a cross-sectional study
Authors
Ikumi Yanagita
Yuya Fujihara
Chikayo Iwaya
Yuichi Kitajima
Misuzu Tajima
Masanao Honda
Yuji Teruya
Hideko Asakawa
Tomoko Ito
Terumi Eda
Noriko Yamaguchi
Yumi Kayashima
Mihoko Yoshimoto
Mayumi Harada
Shoji Yoshimoto
Eiji Aida
Toshihiko Yanase
Hajime Nawata
Kazuo Muta
Publication date
01-12-2020
Publisher
BioMed Central
Published in
BMC Geriatrics / Issue 1/2020
Electronic ISSN: 1471-2318
DOI
https://doi.org/10.1186/s12877-020-01601-z

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