Relative leucocyte telomere length is associated with incident end-stage kidney disease and rapid decline of kidney function in type 2 diabetes : analysis from the Hong Kong Diabetes Register

Feifei Cheng; Andrea O. Luk; Hongjiang Wu; Claudia H. T. Tam; Cadmon K. P. Lim; Baoqi Fan; Guozhi Jiang; Luke Carroll; Aimin Yang; Eric S. H. Lau; Alex C. W. Ng; Heung Man Lee; Elaine Chow; Alice P. S. Kong; Anthony C. Keech; Mugdha V. Joglekar; Wing Yee So; Anandwardhan A. Hardikar; Juliana C. N. Chan; Alicia J. Jenkins; Ronald C. W. Ma

doi:10.1007/s00125-021-05613-1

Relative leucocyte telomere length is associated with incident end-stage kidney disease and rapid decline of kidney function in type 2 diabetes : analysis from the Hong Kong Diabetes Register

Feifei Cheng, Andrea O. Luk, Hongjiang Wu, Claudia H. T. Tam, Cadmon K. P. Lim, Baoqi Fan, Guozhi Jiang, Luke Carroll, Aimin Yang, Eric S. H. Lau, Alex C. W. Ng, Heung Man Lee, Elaine Chow, Alice P. S. Kong, Anthony C. Keech, Mugdha V. Joglekar, Wing Yee So, Anandwardhan A. Hardikar, Juliana C. N. Chan, Alicia J. JenkinsRonald C. W. Ma

Western Sydney University

Research output: Contribution to journal › Article › peer-review

15 Citations (Scopus)

Abstract

Aims/hypothesis: Few large-scale prospective studies have investigated associations between relative leucocyte telomere length (rLTL) and kidney dysfunction in individuals with type 2 diabetes. We examined relationships between rLTL and incident end-stage kidney disease (ESKD) and the slope of eGFR decline in Chinese individuals with type 2 diabetes. Methods: We studied 4085 Chinese individuals with type 2 diabetes observed between 1995 and 2007 in the Hong Kong Diabetes Register with stored baseline DNA and available follow-up data. rLTL was measured using quantitative PCR. ESKD was diagnosed based on the ICD-9 code and eGFR. Results: In this cohort (mean Â± SD age 54.3 Â± 12.6Â years) followed up for 14.1 Â± 5.3Â years, 564 individuals developed incident ESKD and had shorter rLTL at baseline (4.2 Â± 1.2 vs 4.7 Â± 1.2, p < 0.001) than the non-progressors (n = 3521). On Cox regression analysis, each ∆∆Ct decrease in rLTL was associated with an increased risk of incident ESKD (HR 1.21 [95% CI 1.13, 1.30], p < 0.001); the association remained significant after adjusting for baseline age, sex, HbA1c, lipids, renal function and other risk factors (HR 1.11 [95% CI 1.03, 1.19], p = 0.007). Shorter rLTL at baseline was associated with rapid decline in eGFR (>4% per year) during follow-up (unadjusted OR 1.22 [95% CI 1.15, 1.30], p < 0.001; adjusted OR 1.09 [95% CI 1.01, 1.17], p = 0.024). Conclusions/interpretation: rLTL is independently associated with incident ESKD and rapid eGFR loss in individuals with type 2 diabetes. Telomere length may be a useful biomarker for the progression of kidney function and ESKD in type 2 diabetes. Graphical abstract: [Figure not available: see fulltext.]

Original language	English
Pages (from-to)	375-386
Number of pages	12
Journal	Diabetologia
Volume	65
Issue number	2
DOIs	https://doi.org/10.1007/s00125-021-05613-1
Publication status	Published - 2022

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10.1007/s00125-021-05613-1

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Cheng, F., Luk, A. O., Wu, H., Tam, C. H. T., Lim, C. K. P., Fan, B., Jiang, G., Carroll, L., Yang, A., Lau, E. S. H., Ng, A. C. W., Lee, H. M., Chow, E., Kong, A. P. S., Keech, A. C., Joglekar, M. V., So, W. Y., Hardikar, A. A., Chan, J. C. N., ... Ma, R. C. W. (2022). Relative leucocyte telomere length is associated with incident end-stage kidney disease and rapid decline of kidney function in type 2 diabetes : analysis from the Hong Kong Diabetes Register. Diabetologia, 65(2), 375-386. https://doi.org/10.1007/s00125-021-05613-1

@article{b461e9f37a5a4786b91bf37019634858,

title = "Relative leucocyte telomere length is associated with incident end-stage kidney disease and rapid decline of kidney function in type 2 diabetes : analysis from the Hong Kong Diabetes Register",

abstract = "Aims/hypothesis: Few large-scale prospective studies have investigated associations between relative leucocyte telomere length (rLTL) and kidney dysfunction in individuals with type 2 diabetes. We examined relationships between rLTL and incident end-stage kidney disease (ESKD) and the slope of eGFR decline in Chinese individuals with type 2 diabetes. Methods: We studied 4085 Chinese individuals with type 2 diabetes observed between 1995 and 2007 in the Hong Kong Diabetes Register with stored baseline DNA and available follow-up data. rLTL was measured using quantitative PCR. ESKD was diagnosed based on the ICD-9 code and eGFR. Results: In this cohort (mean {\^A}± SD age 54.3 {\^A}± 12.6{\^A} years) followed up for 14.1 {\^A}± 5.3{\^A} years, 564 individuals developed incident ESKD and had shorter rLTL at baseline (4.2 {\^A}± 1.2 vs 4.7 {\^A}± 1.2, p < 0.001) than the non-progressors (n = 3521). On Cox regression analysis, each ∆∆Ct decrease in rLTL was associated with an increased risk of incident ESKD (HR 1.21 [95% CI 1.13, 1.30], p < 0.001); the association remained significant after adjusting for baseline age, sex, HbA1c, lipids, renal function and other risk factors (HR 1.11 [95% CI 1.03, 1.19], p = 0.007). Shorter rLTL at baseline was associated with rapid decline in eGFR (>4% per year) during follow-up (unadjusted OR 1.22 [95% CI 1.15, 1.30], p < 0.001; adjusted OR 1.09 [95% CI 1.01, 1.17], p = 0.024). Conclusions/interpretation: rLTL is independently associated with incident ESKD and rapid eGFR loss in individuals with type 2 diabetes. Telomere length may be a useful biomarker for the progression of kidney function and ESKD in type 2 diabetes. Graphical abstract: [Figure not available: see fulltext.]",

author = "Feifei Cheng and Luk, {Andrea O.} and Hongjiang Wu and Tam, {Claudia H. T.} and Lim, {Cadmon K. P.} and Baoqi Fan and Guozhi Jiang and Luke Carroll and Aimin Yang and Lau, {Eric S. H.} and Ng, {Alex C. W.} and Lee, {Heung Man} and Elaine Chow and Kong, {Alice P. S.} and Keech, {Anthony C.} and Joglekar, {Mugdha V.} and So, {Wing Yee} and Hardikar, {Anandwardhan A.} and Chan, {Juliana C. N.} and Jenkins, {Alicia J.} and Ma, {Ronald C. W.}",

year = "2022",

doi = "10.1007/s00125-021-05613-1",

language = "English",

volume = "65",

pages = "375--386",

journal = "Diabetologia",

issn = "1432-0428",

publisher = "Springer Science and Business Media Deutschland GmbH",

number = "2",

}

Cheng, F, Luk, AO, Wu, H, Tam, CHT, Lim, CKP, Fan, B, Jiang, G, Carroll, L, Yang, A, Lau, ESH, Ng, ACW, Lee, HM, Chow, E, Kong, APS, Keech, AC, Joglekar, MV, So, WY, Hardikar, AA, Chan, JCN, Jenkins, AJ & Ma, RCW 2022, 'Relative leucocyte telomere length is associated with incident end-stage kidney disease and rapid decline of kidney function in type 2 diabetes : analysis from the Hong Kong Diabetes Register', Diabetologia, vol. 65, no. 2, pp. 375-386. https://doi.org/10.1007/s00125-021-05613-1

TY - JOUR

T1 - Relative leucocyte telomere length is associated with incident end-stage kidney disease and rapid decline of kidney function in type 2 diabetes : analysis from the Hong Kong Diabetes Register

AU - Cheng, Feifei

AU - Luk, Andrea O.

AU - Wu, Hongjiang

AU - Tam, Claudia H. T.

AU - Lim, Cadmon K. P.

AU - Fan, Baoqi

AU - Jiang, Guozhi

AU - Carroll, Luke

AU - Yang, Aimin

AU - Lau, Eric S. H.

AU - Ng, Alex C. W.

AU - Lee, Heung Man

AU - Chow, Elaine

AU - Kong, Alice P. S.

AU - Keech, Anthony C.

AU - Joglekar, Mugdha V.

AU - So, Wing Yee

AU - Hardikar, Anandwardhan A.

AU - Chan, Juliana C. N.

AU - Jenkins, Alicia J.

AU - Ma, Ronald C. W.

PY - 2022

Y1 - 2022

N2 - Aims/hypothesis: Few large-scale prospective studies have investigated associations between relative leucocyte telomere length (rLTL) and kidney dysfunction in individuals with type 2 diabetes. We examined relationships between rLTL and incident end-stage kidney disease (ESKD) and the slope of eGFR decline in Chinese individuals with type 2 diabetes. Methods: We studied 4085 Chinese individuals with type 2 diabetes observed between 1995 and 2007 in the Hong Kong Diabetes Register with stored baseline DNA and available follow-up data. rLTL was measured using quantitative PCR. ESKD was diagnosed based on the ICD-9 code and eGFR. Results: In this cohort (mean Â± SD age 54.3 Â± 12.6Â years) followed up for 14.1 Â± 5.3Â years, 564 individuals developed incident ESKD and had shorter rLTL at baseline (4.2 Â± 1.2 vs 4.7 Â± 1.2, p < 0.001) than the non-progressors (n = 3521). On Cox regression analysis, each ∆∆Ct decrease in rLTL was associated with an increased risk of incident ESKD (HR 1.21 [95% CI 1.13, 1.30], p < 0.001); the association remained significant after adjusting for baseline age, sex, HbA1c, lipids, renal function and other risk factors (HR 1.11 [95% CI 1.03, 1.19], p = 0.007). Shorter rLTL at baseline was associated with rapid decline in eGFR (>4% per year) during follow-up (unadjusted OR 1.22 [95% CI 1.15, 1.30], p < 0.001; adjusted OR 1.09 [95% CI 1.01, 1.17], p = 0.024). Conclusions/interpretation: rLTL is independently associated with incident ESKD and rapid eGFR loss in individuals with type 2 diabetes. Telomere length may be a useful biomarker for the progression of kidney function and ESKD in type 2 diabetes. Graphical abstract: [Figure not available: see fulltext.]

AB - Aims/hypothesis: Few large-scale prospective studies have investigated associations between relative leucocyte telomere length (rLTL) and kidney dysfunction in individuals with type 2 diabetes. We examined relationships between rLTL and incident end-stage kidney disease (ESKD) and the slope of eGFR decline in Chinese individuals with type 2 diabetes. Methods: We studied 4085 Chinese individuals with type 2 diabetes observed between 1995 and 2007 in the Hong Kong Diabetes Register with stored baseline DNA and available follow-up data. rLTL was measured using quantitative PCR. ESKD was diagnosed based on the ICD-9 code and eGFR. Results: In this cohort (mean Â± SD age 54.3 Â± 12.6Â years) followed up for 14.1 Â± 5.3Â years, 564 individuals developed incident ESKD and had shorter rLTL at baseline (4.2 Â± 1.2 vs 4.7 Â± 1.2, p < 0.001) than the non-progressors (n = 3521). On Cox regression analysis, each ∆∆Ct decrease in rLTL was associated with an increased risk of incident ESKD (HR 1.21 [95% CI 1.13, 1.30], p < 0.001); the association remained significant after adjusting for baseline age, sex, HbA1c, lipids, renal function and other risk factors (HR 1.11 [95% CI 1.03, 1.19], p = 0.007). Shorter rLTL at baseline was associated with rapid decline in eGFR (>4% per year) during follow-up (unadjusted OR 1.22 [95% CI 1.15, 1.30], p < 0.001; adjusted OR 1.09 [95% CI 1.01, 1.17], p = 0.024). Conclusions/interpretation: rLTL is independently associated with incident ESKD and rapid eGFR loss in individuals with type 2 diabetes. Telomere length may be a useful biomarker for the progression of kidney function and ESKD in type 2 diabetes. Graphical abstract: [Figure not available: see fulltext.]

UR - https://hdl.handle.net/1959.7/uws:65370

U2 - 10.1007/s00125-021-05613-1

DO - 10.1007/s00125-021-05613-1

M3 - Article

SN - 1432-0428

SN - 0012-186X

VL - 65

SP - 375

EP - 386

JO - Diabetologia

JF - Diabetologia

IS - 2

ER -

Relative leucocyte telomere length is associated with incident end-stage kidney disease and rapid decline of kidney function in type 2 diabetes : analysis from the Hong Kong Diabetes Register

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