Elevation of a Novel Angiogenic Factor, Leucine-Rich-α2-Glycoprotein (LRG1), Is Associated With Arterial Stiffness, Endothelial Dysfunction, and Peripheral Arterial Disease in Patients With Type 2 Diabetes
Context: Increased arterial stiffness and endothelial dysfunction are associated with peripheral arterial disease (PAD). Leucine-rich-α2-glycoprotein (LRG1) is a proangiogenic factor involved in regulation of the TGFβ signaling pathway. Objective: This study in patients with type 2 diabetes mellitus...
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| Veröffentlicht in: | The journal of clinical endocrinology and metabolism 2015-04, Vol.100 (4), p.1586-1593 |
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| creator | Pek, Sharon L. T Tavintharan, S Wang, Xiaomeng Lim, Su Chi Woon, Kaing Yeoh, Lee Ying Ng, Xiaowei Liu, Jianjun Sum, Chee Fang |
| description | Context:
Increased arterial stiffness and endothelial dysfunction are associated with peripheral arterial disease (PAD). Leucine-rich-α2-glycoprotein (LRG1) is a proangiogenic factor involved in regulation of the TGFβ signaling pathway.
Objective:
This study in patients with type 2 diabetes mellitus explored the associations of plasma LRG1 with arterial stiffness, endothelial function, and PAD.
Design:
Based on the ankle brachial index (ABI), patients were classified as having PAD (ABI ≤ 0.9) or as being borderline abnormal (ABI, 0.91–0.99) or normal (ABI, 1.00–1.40). LRG1 was measured by immunoassay; arterial stiffness, by carotid-femoral pulse-wave velocity and augmentation index; and endothelial function, by laser Doppler flowmetry.
Results:
A total of 2058 patients with type 2 diabetes mellitus were recruited. Mean age (1 SD) was 57.4 (0.2) years. Patients with PAD (n = 258) had significantly higher LRG1 compared to patients with borderline ABI and patients without PAD (19.00 [13.50] vs 17.35 [13.30] and 15.28 [10.40] μg/mL, respectively; P < .0001). Multiple regression analysis revealed that female gender (P < .0001), non-Chinese ethnicity (P < .0001), higher waist circumference (P = .017), lower estimated glomerular filtration rate (P < .0001), higher urine albumin-creatinine ratio (P = .009), lower ABI (P < .0001), higher pulse wave velocity (P = .040), and poorer endothelium-dependent vasodilation (P = .007) were independent significant predictors of higher plasma LRG1 levels. A generalized linear model showed that a 1-SD increase in log LRG1 was associated with an odds ratio of 4.072 (95% confidence interval, 1.889–8.777; P < .0001) for prevalence of PAD, after adjustment for traditional risk factors.
Conclusions:
Higher LRG1 is a significant predictor for arterial stiffness, endothelial function, and PAD. The pathobiological basis and the temporal relationships of these associations need to be explored by further mechanistic and prospective studies to understand the clinical significance of these findings. |
| doi_str_mv | 10.1210/jc.2014-3855 |
| format | Article |
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Increased arterial stiffness and endothelial dysfunction are associated with peripheral arterial disease (PAD). Leucine-rich-α2-glycoprotein (LRG1) is a proangiogenic factor involved in regulation of the TGFβ signaling pathway.
Objective:
This study in patients with type 2 diabetes mellitus explored the associations of plasma LRG1 with arterial stiffness, endothelial function, and PAD.
Design:
Based on the ankle brachial index (ABI), patients were classified as having PAD (ABI ≤ 0.9) or as being borderline abnormal (ABI, 0.91–0.99) or normal (ABI, 1.00–1.40). LRG1 was measured by immunoassay; arterial stiffness, by carotid-femoral pulse-wave velocity and augmentation index; and endothelial function, by laser Doppler flowmetry.
Results:
A total of 2058 patients with type 2 diabetes mellitus were recruited. Mean age (1 SD) was 57.4 (0.2) years. Patients with PAD (n = 258) had significantly higher LRG1 compared to patients with borderline ABI and patients without PAD (19.00 [13.50] vs 17.35 [13.30] and 15.28 [10.40] μg/mL, respectively; P < .0001). Multiple regression analysis revealed that female gender (P < .0001), non-Chinese ethnicity (P < .0001), higher waist circumference (P = .017), lower estimated glomerular filtration rate (P < .0001), higher urine albumin-creatinine ratio (P = .009), lower ABI (P < .0001), higher pulse wave velocity (P = .040), and poorer endothelium-dependent vasodilation (P = .007) were independent significant predictors of higher plasma LRG1 levels. A generalized linear model showed that a 1-SD increase in log LRG1 was associated with an odds ratio of 4.072 (95% confidence interval, 1.889–8.777; P < .0001) for prevalence of PAD, after adjustment for traditional risk factors.
Conclusions:
Higher LRG1 is a significant predictor for arterial stiffness, endothelial function, and PAD. The pathobiological basis and the temporal relationships of these associations need to be explored by further mechanistic and prospective studies to understand the clinical significance of these findings.]]></description><identifier>ISSN: 0021-972X</identifier><identifier>EISSN: 1945-7197</identifier><identifier>DOI: 10.1210/jc.2014-3855</identifier><identifier>PMID: 25636050</identifier><language>eng</language><publisher>United States: Endocrine Society</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Cross-Sectional Studies ; Diabetes Mellitus, Type 2 - blood ; Diabetes Mellitus, Type 2 - complications ; Diabetes Mellitus, Type 2 - diagnosis ; Diabetes Mellitus, Type 2 - physiopathology ; Diabetic Angiopathies - blood ; Diabetic Angiopathies - diagnosis ; Diabetic Angiopathies - physiopathology ; Endothelium, Vascular - physiopathology ; Female ; Glycoproteins - blood ; Humans ; Male ; Middle Aged ; Peripheral Arterial Disease - blood ; Peripheral Arterial Disease - diagnosis ; Peripheral Arterial Disease - physiopathology ; Prognosis ; Up-Regulation ; Vascular Stiffness ; Young Adult</subject><ispartof>The journal of clinical endocrinology and metabolism, 2015-04, Vol.100 (4), p.1586-1593</ispartof><rights>Copyright © 2015 by the Endocrine Society</rights><rights>Copyright © 2015 by The Endocrine Society</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3337-637005695ba998ef26d024e3ae8062638290ff4dc52162eb90136809ca6714853</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25636050$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pek, Sharon L. T</creatorcontrib><creatorcontrib>Tavintharan, S</creatorcontrib><creatorcontrib>Wang, Xiaomeng</creatorcontrib><creatorcontrib>Lim, Su Chi</creatorcontrib><creatorcontrib>Woon, Kaing</creatorcontrib><creatorcontrib>Yeoh, Lee Ying</creatorcontrib><creatorcontrib>Ng, Xiaowei</creatorcontrib><creatorcontrib>Liu, Jianjun</creatorcontrib><creatorcontrib>Sum, Chee Fang</creatorcontrib><title>Elevation of a Novel Angiogenic Factor, Leucine-Rich-α2-Glycoprotein (LRG1), Is Associated With Arterial Stiffness, Endothelial Dysfunction, and Peripheral Arterial Disease in Patients With Type 2 Diabetes</title><title>The journal of clinical endocrinology and metabolism</title><addtitle>J Clin Endocrinol Metab</addtitle><description><![CDATA[Context:
Increased arterial stiffness and endothelial dysfunction are associated with peripheral arterial disease (PAD). Leucine-rich-α2-glycoprotein (LRG1) is a proangiogenic factor involved in regulation of the TGFβ signaling pathway.
Objective:
This study in patients with type 2 diabetes mellitus explored the associations of plasma LRG1 with arterial stiffness, endothelial function, and PAD.
Design:
Based on the ankle brachial index (ABI), patients were classified as having PAD (ABI ≤ 0.9) or as being borderline abnormal (ABI, 0.91–0.99) or normal (ABI, 1.00–1.40). LRG1 was measured by immunoassay; arterial stiffness, by carotid-femoral pulse-wave velocity and augmentation index; and endothelial function, by laser Doppler flowmetry.
Results:
A total of 2058 patients with type 2 diabetes mellitus were recruited. Mean age (1 SD) was 57.4 (0.2) years. Patients with PAD (n = 258) had significantly higher LRG1 compared to patients with borderline ABI and patients without PAD (19.00 [13.50] vs 17.35 [13.30] and 15.28 [10.40] μg/mL, respectively; P < .0001). Multiple regression analysis revealed that female gender (P < .0001), non-Chinese ethnicity (P < .0001), higher waist circumference (P = .017), lower estimated glomerular filtration rate (P < .0001), higher urine albumin-creatinine ratio (P = .009), lower ABI (P < .0001), higher pulse wave velocity (P = .040), and poorer endothelium-dependent vasodilation (P = .007) were independent significant predictors of higher plasma LRG1 levels. A generalized linear model showed that a 1-SD increase in log LRG1 was associated with an odds ratio of 4.072 (95% confidence interval, 1.889–8.777; P < .0001) for prevalence of PAD, after adjustment for traditional risk factors.
Conclusions:
Higher LRG1 is a significant predictor for arterial stiffness, endothelial function, and PAD. The pathobiological basis and the temporal relationships of these associations need to be explored by further mechanistic and prospective studies to understand the clinical significance of these findings.]]></description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Cross-Sectional Studies</subject><subject>Diabetes Mellitus, Type 2 - blood</subject><subject>Diabetes Mellitus, Type 2 - complications</subject><subject>Diabetes Mellitus, Type 2 - diagnosis</subject><subject>Diabetes Mellitus, Type 2 - physiopathology</subject><subject>Diabetic Angiopathies - blood</subject><subject>Diabetic Angiopathies - diagnosis</subject><subject>Diabetic Angiopathies - physiopathology</subject><subject>Endothelium, Vascular - physiopathology</subject><subject>Female</subject><subject>Glycoproteins - blood</subject><subject>Humans</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Peripheral Arterial Disease - blood</subject><subject>Peripheral Arterial Disease - diagnosis</subject><subject>Peripheral Arterial Disease - physiopathology</subject><subject>Prognosis</subject><subject>Up-Regulation</subject><subject>Vascular Stiffness</subject><subject>Young Adult</subject><issn>0021-972X</issn><issn>1945-7197</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkc1uEzEUhUcIRENhxxp5WaS4-Gc8P8uoTUOlCKpSBDvL8dzpOLh2sD2t8li8SJ8Jj1K6whvL9373-OqconhPySlllHza6lNGaIl5I8SLYkbbUuCatvXLYkYIo7it2c-j4k2MW5KxUvDXxRETFa-IILPicWnhXiXjHfI9UuiLvweLFu7W-FtwRqMLpZMPc7SGURsH-NroAT_-YXhl99rvgk9gHDpZX6_oxzm6jGgRo9dGJejQD5MGtAgJglEWfUum7x3EOEdL1_k0gJ3K5_vYj05PK8yRch26yvhugJB7z7PnJoKKgPJXV3lbcCke1G_2O0As99UGEsS3xate2Qjvnu7j4vvF8ubsM15_XV2eLdZYc85rXPGaEFG1YqPatoGeVR1hJXAFDalYxRvWkr4vOy0YrRhsWkJ51ZBWq6qmZSP4cXFy0M0G_B4hJnlnogZrlQM_Rkkzx6jglGZ0fkB18DEG6OUumDsV9pISOSUot1pOCcopwYx_eFIeN3fQPcP_IstAeQAevM3uxF92fIAgB1A2DZLkU1Z1g7OiIGV-4alS5zF-GIPsvQ45yl3IWcitH4PLVv1_m7-kSLfG</recordid><startdate>201504</startdate><enddate>201504</enddate><creator>Pek, Sharon L. T</creator><creator>Tavintharan, S</creator><creator>Wang, Xiaomeng</creator><creator>Lim, Su Chi</creator><creator>Woon, Kaing</creator><creator>Yeoh, Lee Ying</creator><creator>Ng, Xiaowei</creator><creator>Liu, Jianjun</creator><creator>Sum, Chee Fang</creator><general>Endocrine Society</general><general>Copyright by The Endocrine Society</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>7X8</scope></search><sort><creationdate>201504</creationdate><title>Elevation of a Novel Angiogenic Factor, Leucine-Rich-α2-Glycoprotein (LRG1), Is Associated With Arterial Stiffness, Endothelial Dysfunction, and Peripheral Arterial Disease in Patients With Type 2 Diabetes</title><author>Pek, Sharon L. T ; Tavintharan, S ; Wang, Xiaomeng ; Lim, Su Chi ; Woon, Kaing ; Yeoh, Lee Ying ; Ng, Xiaowei ; Liu, Jianjun ; Sum, Chee Fang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3337-637005695ba998ef26d024e3ae8062638290ff4dc52162eb90136809ca6714853</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Cross-Sectional Studies</topic><topic>Diabetes Mellitus, Type 2 - blood</topic><topic>Diabetes Mellitus, Type 2 - complications</topic><topic>Diabetes Mellitus, Type 2 - diagnosis</topic><topic>Diabetes Mellitus, Type 2 - physiopathology</topic><topic>Diabetic Angiopathies - blood</topic><topic>Diabetic Angiopathies - diagnosis</topic><topic>Diabetic Angiopathies - physiopathology</topic><topic>Endothelium, Vascular - physiopathology</topic><topic>Female</topic><topic>Glycoproteins - blood</topic><topic>Humans</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Peripheral Arterial Disease - blood</topic><topic>Peripheral Arterial Disease - diagnosis</topic><topic>Peripheral Arterial Disease - physiopathology</topic><topic>Prognosis</topic><topic>Up-Regulation</topic><topic>Vascular Stiffness</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pek, Sharon L. T</creatorcontrib><creatorcontrib>Tavintharan, S</creatorcontrib><creatorcontrib>Wang, Xiaomeng</creatorcontrib><creatorcontrib>Lim, Su Chi</creatorcontrib><creatorcontrib>Woon, Kaing</creatorcontrib><creatorcontrib>Yeoh, Lee Ying</creatorcontrib><creatorcontrib>Ng, Xiaowei</creatorcontrib><creatorcontrib>Liu, Jianjun</creatorcontrib><creatorcontrib>Sum, Chee Fang</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>The journal of clinical endocrinology and metabolism</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pek, Sharon L. T</au><au>Tavintharan, S</au><au>Wang, Xiaomeng</au><au>Lim, Su Chi</au><au>Woon, Kaing</au><au>Yeoh, Lee Ying</au><au>Ng, Xiaowei</au><au>Liu, Jianjun</au><au>Sum, Chee Fang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Elevation of a Novel Angiogenic Factor, Leucine-Rich-α2-Glycoprotein (LRG1), Is Associated With Arterial Stiffness, Endothelial Dysfunction, and Peripheral Arterial Disease in Patients With Type 2 Diabetes</atitle><jtitle>The journal of clinical endocrinology and metabolism</jtitle><addtitle>J Clin Endocrinol Metab</addtitle><date>2015-04</date><risdate>2015</risdate><volume>100</volume><issue>4</issue><spage>1586</spage><epage>1593</epage><pages>1586-1593</pages><issn>0021-972X</issn><eissn>1945-7197</eissn><abstract><![CDATA[Context:
Increased arterial stiffness and endothelial dysfunction are associated with peripheral arterial disease (PAD). Leucine-rich-α2-glycoprotein (LRG1) is a proangiogenic factor involved in regulation of the TGFβ signaling pathway.
Objective:
This study in patients with type 2 diabetes mellitus explored the associations of plasma LRG1 with arterial stiffness, endothelial function, and PAD.
Design:
Based on the ankle brachial index (ABI), patients were classified as having PAD (ABI ≤ 0.9) or as being borderline abnormal (ABI, 0.91–0.99) or normal (ABI, 1.00–1.40). LRG1 was measured by immunoassay; arterial stiffness, by carotid-femoral pulse-wave velocity and augmentation index; and endothelial function, by laser Doppler flowmetry.
Results:
A total of 2058 patients with type 2 diabetes mellitus were recruited. Mean age (1 SD) was 57.4 (0.2) years. Patients with PAD (n = 258) had significantly higher LRG1 compared to patients with borderline ABI and patients without PAD (19.00 [13.50] vs 17.35 [13.30] and 15.28 [10.40] μg/mL, respectively; P < .0001). Multiple regression analysis revealed that female gender (P < .0001), non-Chinese ethnicity (P < .0001), higher waist circumference (P = .017), lower estimated glomerular filtration rate (P < .0001), higher urine albumin-creatinine ratio (P = .009), lower ABI (P < .0001), higher pulse wave velocity (P = .040), and poorer endothelium-dependent vasodilation (P = .007) were independent significant predictors of higher plasma LRG1 levels. A generalized linear model showed that a 1-SD increase in log LRG1 was associated with an odds ratio of 4.072 (95% confidence interval, 1.889–8.777; P < .0001) for prevalence of PAD, after adjustment for traditional risk factors.
Conclusions:
Higher LRG1 is a significant predictor for arterial stiffness, endothelial function, and PAD. The pathobiological basis and the temporal relationships of these associations need to be explored by further mechanistic and prospective studies to understand the clinical significance of these findings.]]></abstract><cop>United States</cop><pub>Endocrine Society</pub><pmid>25636050</pmid><doi>10.1210/jc.2014-3855</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0021-972X |
| ispartof | The journal of clinical endocrinology and metabolism, 2015-04, Vol.100 (4), p.1586-1593 |
| issn | 0021-972X 1945-7197 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1671215311 |
| source | Journals@Ovid Ovid Autoload; Oxford University Press Journals All Titles (1996-Current); MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Adult Aged Aged, 80 and over Cross-Sectional Studies Diabetes Mellitus, Type 2 - blood Diabetes Mellitus, Type 2 - complications Diabetes Mellitus, Type 2 - diagnosis Diabetes Mellitus, Type 2 - physiopathology Diabetic Angiopathies - blood Diabetic Angiopathies - diagnosis Diabetic Angiopathies - physiopathology Endothelium, Vascular - physiopathology Female Glycoproteins - blood Humans Male Middle Aged Peripheral Arterial Disease - blood Peripheral Arterial Disease - diagnosis Peripheral Arterial Disease - physiopathology Prognosis Up-Regulation Vascular Stiffness Young Adult |
| title | Elevation of a Novel Angiogenic Factor, Leucine-Rich-α2-Glycoprotein (LRG1), Is Associated With Arterial Stiffness, Endothelial Dysfunction, and Peripheral Arterial Disease in Patients With Type 2 Diabetes |
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