Shortened Leukocyte Telomere Length Is Associated With Glycemic Progression in Type 2 Diabetes: A Prospective and Mendelian Randomization Analysis
Several studies support associations between relative leukocyte telomere length (rLTL), a biomarker of biological aging and type 2 diabetes. This study investigates the relationship between rLTL and the risk of glycemic progression in patients with type 2 diabetes. In this cohort study, consecutive...
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| Veröffentlicht in: | Diabetes care 2022-03, Vol.45 (3), p.701-709 |
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| creator | Cheng, Feifei Luk, Andrea O Shi, Mai Huang, Chuiguo Jiang, Guozhi Yang, Aimin Wu, Hongjiang Lim, Cadmon K P Tam, Claudia H T Fan, Baoqi Lau, Eric S H Ng, Alex C W Wong, Kwun Kiu Carroll, Luke Lee, Heung Man Kong, Alice P Keech, Anthony C Chow, Elaine Joglekar, Mugdha V Tsui, Stephen K W So, Wing Yee So, Hon Cheong Hardikar, Anandwardhan A Jenkins, Alicia J Chan, Juliana C N Ma, Ronald C W |
| description | Several studies support associations between relative leukocyte telomere length (rLTL), a biomarker of biological aging and type 2 diabetes. This study investigates the relationship between rLTL and the risk of glycemic progression in patients with type 2 diabetes.
In this cohort study, consecutive Chinese patients with type 2 diabetes (N = 5,506) from the Hong Kong Diabetes Register with stored baseline DNA and available follow-up data were studied. rLTL was measured using quantitative PCR. Glycemic progression was defined as the new need for exogenous insulin.
The mean (SD) age of the 5,349 subjects was 57.0 (13.3) years, and mean (SD) follow-up was 8.8 (5.4) years. Baseline rLTL was significantly shorter in the 1,803 subjects who progressed to insulin requirement compared with the remaining subjects (4.43 ± 1.16 vs. 4.69 ± 1.20). Shorter rLTL was associated with a higher risk of glycemic progression (hazard ratio [95% CI] for each unit decrease [to ∼0.2 kilobases]: 1.10 [1.06-1.14]), which remained significant after adjusting for confounders. Baseline rLTL was independently associated with glycemic exposure during follow-up (β = -0.05 [-0.06 to -0.04]). Each 1-kilobase decrease in absolute LTL was on average associated with a 1.69-fold higher risk of diabetes progression (95% CI 1.35-2.11). Two-sample Mendelian randomization analysis showed per 1-unit genetically decreased rLTL was associated with a 1.38-fold higher risk of diabetes progression (95% CI 1.12-1.70).
Shorter rLTL was significantly associated with an increased risk of glycemic progression in individuals with type 2 diabetes, independent of established risk factors. Telomere length may be a useful biomarker for glycemic progression in people with type 2 diabetes. |
| doi_str_mv | 10.2337/dc21-1609 |
| format | Article |
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In this cohort study, consecutive Chinese patients with type 2 diabetes (N = 5,506) from the Hong Kong Diabetes Register with stored baseline DNA and available follow-up data were studied. rLTL was measured using quantitative PCR. Glycemic progression was defined as the new need for exogenous insulin.
The mean (SD) age of the 5,349 subjects was 57.0 (13.3) years, and mean (SD) follow-up was 8.8 (5.4) years. Baseline rLTL was significantly shorter in the 1,803 subjects who progressed to insulin requirement compared with the remaining subjects (4.43 ± 1.16 vs. 4.69 ± 1.20). Shorter rLTL was associated with a higher risk of glycemic progression (hazard ratio [95% CI] for each unit decrease [to ∼0.2 kilobases]: 1.10 [1.06-1.14]), which remained significant after adjusting for confounders. Baseline rLTL was independently associated with glycemic exposure during follow-up (β = -0.05 [-0.06 to -0.04]). Each 1-kilobase decrease in absolute LTL was on average associated with a 1.69-fold higher risk of diabetes progression (95% CI 1.35-2.11). Two-sample Mendelian randomization analysis showed per 1-unit genetically decreased rLTL was associated with a 1.38-fold higher risk of diabetes progression (95% CI 1.12-1.70).
Shorter rLTL was significantly associated with an increased risk of glycemic progression in individuals with type 2 diabetes, independent of established risk factors. Telomere length may be a useful biomarker for glycemic progression in people with type 2 diabetes.</description><identifier>ISSN: 0149-5992</identifier><identifier>EISSN: 1935-5548</identifier><identifier>DOI: 10.2337/dc21-1609</identifier><identifier>PMID: 35085380</identifier><language>eng</language><publisher>United States: American Diabetes Association</publisher><subject>Aging ; Biomarkers ; Cohort Studies ; Deoxyribonucleic acid ; Diabetes ; Diabetes mellitus ; Diabetes mellitus (non-insulin dependent) ; Diabetes Mellitus, Type 2 - genetics ; DNA ; Health risks ; Humans ; Insulin ; Leukocytes ; Mendelian Randomization Analysis ; Middle Aged ; Pathophysiology/Complications ; Prospective Studies ; Randomization ; Research design ; Risk analysis ; Risk factors ; Telomere - genetics ; Telomere Shortening ; Telomeres</subject><ispartof>Diabetes care, 2022-03, Vol.45 (3), p.701-709</ispartof><rights>2022 by the American Diabetes Association.</rights><rights>Copyright American Diabetes Association Mar 2022</rights><rights>2022 by the American Diabetes Association 2022</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c403t-b6ea6c23bed942e66ee5886ebf6cf3fae8a62ee71479b937b3a2323fc018e46c3</citedby><cites>FETCH-LOGICAL-c403t-b6ea6c23bed942e66ee5886ebf6cf3fae8a62ee71479b937b3a2323fc018e46c3</cites><orcidid>0000-0002-1227-803X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,315,782,786,887,27933,27934</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35085380$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cheng, Feifei</creatorcontrib><creatorcontrib>Luk, Andrea O</creatorcontrib><creatorcontrib>Shi, Mai</creatorcontrib><creatorcontrib>Huang, Chuiguo</creatorcontrib><creatorcontrib>Jiang, Guozhi</creatorcontrib><creatorcontrib>Yang, Aimin</creatorcontrib><creatorcontrib>Wu, Hongjiang</creatorcontrib><creatorcontrib>Lim, Cadmon K P</creatorcontrib><creatorcontrib>Tam, Claudia H T</creatorcontrib><creatorcontrib>Fan, Baoqi</creatorcontrib><creatorcontrib>Lau, Eric S H</creatorcontrib><creatorcontrib>Ng, Alex C W</creatorcontrib><creatorcontrib>Wong, Kwun Kiu</creatorcontrib><creatorcontrib>Carroll, Luke</creatorcontrib><creatorcontrib>Lee, Heung Man</creatorcontrib><creatorcontrib>Kong, Alice P</creatorcontrib><creatorcontrib>Keech, Anthony C</creatorcontrib><creatorcontrib>Chow, Elaine</creatorcontrib><creatorcontrib>Joglekar, Mugdha V</creatorcontrib><creatorcontrib>Tsui, Stephen K W</creatorcontrib><creatorcontrib>So, Wing Yee</creatorcontrib><creatorcontrib>So, Hon Cheong</creatorcontrib><creatorcontrib>Hardikar, Anandwardhan A</creatorcontrib><creatorcontrib>Jenkins, Alicia J</creatorcontrib><creatorcontrib>Chan, Juliana C N</creatorcontrib><creatorcontrib>Ma, Ronald C W</creatorcontrib><title>Shortened Leukocyte Telomere Length Is Associated With Glycemic Progression in Type 2 Diabetes: A Prospective and Mendelian Randomization Analysis</title><title>Diabetes care</title><addtitle>Diabetes Care</addtitle><description>Several studies support associations between relative leukocyte telomere length (rLTL), a biomarker of biological aging and type 2 diabetes. This study investigates the relationship between rLTL and the risk of glycemic progression in patients with type 2 diabetes.
In this cohort study, consecutive Chinese patients with type 2 diabetes (N = 5,506) from the Hong Kong Diabetes Register with stored baseline DNA and available follow-up data were studied. rLTL was measured using quantitative PCR. Glycemic progression was defined as the new need for exogenous insulin.
The mean (SD) age of the 5,349 subjects was 57.0 (13.3) years, and mean (SD) follow-up was 8.8 (5.4) years. Baseline rLTL was significantly shorter in the 1,803 subjects who progressed to insulin requirement compared with the remaining subjects (4.43 ± 1.16 vs. 4.69 ± 1.20). Shorter rLTL was associated with a higher risk of glycemic progression (hazard ratio [95% CI] for each unit decrease [to ∼0.2 kilobases]: 1.10 [1.06-1.14]), which remained significant after adjusting for confounders. Baseline rLTL was independently associated with glycemic exposure during follow-up (β = -0.05 [-0.06 to -0.04]). Each 1-kilobase decrease in absolute LTL was on average associated with a 1.69-fold higher risk of diabetes progression (95% CI 1.35-2.11). Two-sample Mendelian randomization analysis showed per 1-unit genetically decreased rLTL was associated with a 1.38-fold higher risk of diabetes progression (95% CI 1.12-1.70).
Shorter rLTL was significantly associated with an increased risk of glycemic progression in individuals with type 2 diabetes, independent of established risk factors. Telomere length may be a useful biomarker for glycemic progression in people with type 2 diabetes.</description><subject>Aging</subject><subject>Biomarkers</subject><subject>Cohort Studies</subject><subject>Deoxyribonucleic acid</subject><subject>Diabetes</subject><subject>Diabetes mellitus</subject><subject>Diabetes mellitus (non-insulin dependent)</subject><subject>Diabetes Mellitus, Type 2 - genetics</subject><subject>DNA</subject><subject>Health risks</subject><subject>Humans</subject><subject>Insulin</subject><subject>Leukocytes</subject><subject>Mendelian Randomization Analysis</subject><subject>Middle Aged</subject><subject>Pathophysiology/Complications</subject><subject>Prospective Studies</subject><subject>Randomization</subject><subject>Research design</subject><subject>Risk analysis</subject><subject>Risk factors</subject><subject>Telomere - genetics</subject><subject>Telomere Shortening</subject><subject>Telomeres</subject><issn>0149-5992</issn><issn>1935-5548</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkcFu1DAQhi1ERZfCgRdAlriUQ8CxHcfhgLRqoVRaBIJFHC3Hmey6JPZiO5XSx-CJcdRSAafRzHzza2Z-hJ6V5BVlrH7dGVoWpSDNA7QqG1YVVcXlQ7QiJW-KqmnoMXoc4xUhhHMpH6FjVhFZMUlW6NfXvQ8JHHR4A9MPb-YEeAuDHyFALrld2uPLiNcxemN1ytx3m0sXw2xgtAZ_Dn4XIEbrHbYOb-cDYIrPrW4hQXyD1wsRD2CSvQasXYc_gutgsNrhLzn1o73RaZleOz3M0cYn6KjXQ4Snd_EEfXv_bnv2odh8urg8W28KwwlLRStAC0NZC13DKQgBUEkpoO2F6VmvQWpBAeqS103bsLplmjLKekNKCVwYdoLe3uoepnaEzoBLQQ_qEOyow6y8turfjrN7tfPXSjalpKzOAqd3AsH_nCAmNdpoYBi0Az9FRQVlUnLJWUZf_Ide-SnkgxeKE05kzUimXt5SJr8sBujvlymJWpxWi9NqcTqzz__e_p78Yy37DTfWprg</recordid><startdate>20220301</startdate><enddate>20220301</enddate><creator>Cheng, Feifei</creator><creator>Luk, Andrea O</creator><creator>Shi, Mai</creator><creator>Huang, Chuiguo</creator><creator>Jiang, Guozhi</creator><creator>Yang, Aimin</creator><creator>Wu, Hongjiang</creator><creator>Lim, Cadmon K P</creator><creator>Tam, Claudia H T</creator><creator>Fan, Baoqi</creator><creator>Lau, Eric S H</creator><creator>Ng, Alex C W</creator><creator>Wong, Kwun Kiu</creator><creator>Carroll, Luke</creator><creator>Lee, Heung Man</creator><creator>Kong, Alice P</creator><creator>Keech, Anthony C</creator><creator>Chow, Elaine</creator><creator>Joglekar, Mugdha V</creator><creator>Tsui, Stephen K W</creator><creator>So, Wing Yee</creator><creator>So, Hon Cheong</creator><creator>Hardikar, Anandwardhan A</creator><creator>Jenkins, Alicia J</creator><creator>Chan, Juliana C N</creator><creator>Ma, Ronald C W</creator><general>American Diabetes Association</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-1227-803X</orcidid></search><sort><creationdate>20220301</creationdate><title>Shortened Leukocyte Telomere Length Is Associated With Glycemic Progression in Type 2 Diabetes: A Prospective and Mendelian Randomization Analysis</title><author>Cheng, Feifei ; 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This study investigates the relationship between rLTL and the risk of glycemic progression in patients with type 2 diabetes.
In this cohort study, consecutive Chinese patients with type 2 diabetes (N = 5,506) from the Hong Kong Diabetes Register with stored baseline DNA and available follow-up data were studied. rLTL was measured using quantitative PCR. Glycemic progression was defined as the new need for exogenous insulin.
The mean (SD) age of the 5,349 subjects was 57.0 (13.3) years, and mean (SD) follow-up was 8.8 (5.4) years. Baseline rLTL was significantly shorter in the 1,803 subjects who progressed to insulin requirement compared with the remaining subjects (4.43 ± 1.16 vs. 4.69 ± 1.20). Shorter rLTL was associated with a higher risk of glycemic progression (hazard ratio [95% CI] for each unit decrease [to ∼0.2 kilobases]: 1.10 [1.06-1.14]), which remained significant after adjusting for confounders. Baseline rLTL was independently associated with glycemic exposure during follow-up (β = -0.05 [-0.06 to -0.04]). Each 1-kilobase decrease in absolute LTL was on average associated with a 1.69-fold higher risk of diabetes progression (95% CI 1.35-2.11). Two-sample Mendelian randomization analysis showed per 1-unit genetically decreased rLTL was associated with a 1.38-fold higher risk of diabetes progression (95% CI 1.12-1.70).
Shorter rLTL was significantly associated with an increased risk of glycemic progression in individuals with type 2 diabetes, independent of established risk factors. Telomere length may be a useful biomarker for glycemic progression in people with type 2 diabetes.</abstract><cop>United States</cop><pub>American Diabetes Association</pub><pmid>35085380</pmid><doi>10.2337/dc21-1609</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-1227-803X</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Diabetes care, 2022-03, Vol.45 (3), p.701-709 |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Aging Biomarkers Cohort Studies Deoxyribonucleic acid Diabetes Diabetes mellitus Diabetes mellitus (non-insulin dependent) Diabetes Mellitus, Type 2 - genetics DNA Health risks Humans Insulin Leukocytes Mendelian Randomization Analysis Middle Aged Pathophysiology/Complications Prospective Studies Randomization Research design Risk analysis Risk factors Telomere - genetics Telomere Shortening Telomeres |
| title | Shortened Leukocyte Telomere Length Is Associated With Glycemic Progression in Type 2 Diabetes: A Prospective and Mendelian Randomization Analysis |
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