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Gurung RL, Liu S, Liu JJ, M Y, Zheng H, Chan C, Ang K, Subramaniam T, Sum CF, Lim SC. Association of plasma angiogenin with risk of major cardiovascular events in type 2 diabetes. Cardiovasc Diabetol 2024; 23:70. [PMID: 38360721 PMCID: PMC10870605 DOI: 10.1186/s12933-024-02156-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2023] [Accepted: 02/07/2024] [Indexed: 02/17/2024] Open
Abstract
BACKGROUND Angiogenin, an enzyme belonging to the ribonucleases A superfamily, plays an important role in vascular biology. Here, we sought to study the association of plasma angiogenin and major adverse cardiovascular events (MACEs) in patients with type 2 diabetes (T2D). METHODS This prospective study included 1083 T2D individuals recruited from a secondary hospital and a primary care facility. The primary outcome was a composite of four-point MACE (nonfatal myocardial infarction, stroke, unstable angina pectoris leading to hospitalization and cardiovascular death). Circulating angiogenin was measured by a proximity extension assay. Cox regression models were used to evaluate the association of baseline plasma angiogenin with the risk of MACE. RESULTS During a median follow-up of 9.3 years, 109 (10%) MACE were identified. Plasma angiogenin was significantly higher in participants with MACE than in those without MACE (P < 0.001). Doubling of plasma angiogenin concentration was associated with a 3.10-fold (95% CI 1.84-5.22) increased risk for MACE. The association was only moderately attenuated after adjustment for demographic and cardiometabolic risk factors (adjusted HR 2.38, 95% CI 1.34-4.23) and remained statistically significant after additional adjustment for estimated glomerular filtration rate (eGFR) and urinary albumin to creatinine ratio (uACR) (adjusted HR 1.90, 95% CI 1.02-3.53). A consistent outcome was obtained when plasma angiogenin was analysed as a categorical variable in tertiles. CONCLUSIONS Plasma angiogenin was associated with the risk of future cardiovascular events in patients with T2D and may be a promising novel biomarker for identifying high-risk T2D patients for early management.
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Affiliation(s)
- Resham L Gurung
- Clinical Research Unit, Khoo Teck Puat Hospital, Singapore, Singapore
- Cardiovascular and Metabolic Disorders Signature Research Program, Duke-NUS Medical School, Singapore, Singapore
| | - Sylvia Liu
- Clinical Research Unit, Khoo Teck Puat Hospital, Singapore, Singapore
| | - Jian-Jun Liu
- Clinical Research Unit, Khoo Teck Puat Hospital, Singapore, Singapore
| | - Yiamunaa M
- Clinical Research Unit, Khoo Teck Puat Hospital, Singapore, Singapore
| | - Huili Zheng
- Clinical Research Unit, Khoo Teck Puat Hospital, Singapore, Singapore
| | - Clara Chan
- Clinical Research Unit, Khoo Teck Puat Hospital, Singapore, Singapore
| | - Keven Ang
- Clinical Research Unit, Khoo Teck Puat Hospital, Singapore, Singapore
| | | | - Chee Fang Sum
- Diabetes Centre, Admiralty Medical Centre, Singapore, Singapore
| | - Su Chi Lim
- Clinical Research Unit, Khoo Teck Puat Hospital, Singapore, Singapore.
- Diabetes Centre, Admiralty Medical Centre, Singapore, Singapore.
- Saw Swee Hock School of Public Heath, Singapore, Singapore.
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore.
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Neelam K, Aung KCY, Ang K, Tavintharan S, Sum CF, Lim SC. Association of Triglyceride Glucose Index with Prevalence and Incidence of Diabetic Retinopathy in a Singaporean Population. Clin Ophthalmol 2023; 17:445-454. [PMID: 36755892 PMCID: PMC9901446 DOI: 10.2147/opth.s382336] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2022] [Accepted: 11/02/2022] [Indexed: 02/05/2023] Open
Abstract
Objective To examine the association of triglyceride glucose (TyG) index (product of fasting triglyceride and glucose) with prevalence and incidence of diabetic retinopathy (DR) in type 2 diabetes. Methods 1339 patients from an ongoing Singapore Study of Macro-angiopathy and Micro-Vascular Reactivity in Type 2 Diabetes (SMART2D) were included in this study. Fasting triglyceride and glucose levels were quantified and color fundus photographs were assessed for DR presence and severity. Logistic regression models were used to evaluate associations of TyG index with DR prevalence and incidence (median follow-up period = 3.2 years). Results Mean TyG index was higher in patients with DR than no DR (9.24±0.7 versus 9.04± 0.6, p<0.001). TyG index was significantly associated with DR prevalence (OR=1.4, CI 1.1-1.7, p=0.002) and incidence (OR=1.8, CI 1.04-2.9, p=0.03), after adjusting for confounders. In a stratified analysis, the association between TyG index and DR prevalence reached significance only in the subgroup with HbA1c levels < 7.0% (OR=2, CI 1.1-3.8, p=0.03). TyG index significantly predicted DR prevalence and incidence with area under receiver operating curve as 0.77 (CI 0.74-0.80, p <0.001) and 0.66 (CI 0.57-0.76, p value <0.01), respectively. Conclusion TyG index is a good predictor for DR prevalence and incidence. It can also be a secondary treatment target for patients with optimally controlled levels of HbA1c.
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Affiliation(s)
- Kumari Neelam
- Department of Ophthalmology and Visual Sciences, Khoo Teck Puat Hospital, Singapore,Singapore Eye Research Institute, Singapore
| | | | - Keven Ang
- Clinical Research Unit, Khoo Teck Puat Hospital, Singapore
| | - Subramaniam Tavintharan
- Clinical Research Unit, Khoo Teck Puat Hospital, Singapore,Diabetes Centre, Admiralty Medical Centre, Singapore
| | - Chee Fang Sum
- Diabetes Centre, Admiralty Medical Centre, Singapore
| | - Su Chi Lim
- Clinical Research Unit, Khoo Teck Puat Hospital, Singapore,Diabetes Centre, Admiralty Medical Centre, Singapore,Saw Swee Hock School of Public Health, National University of Singapore, Singapore,Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore,Correspondence: Su Chi Lim, Clinical Research Unit, Khoo Teck Puat Hospital, 90 Yishun Central, 728828, Singapore, Email
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Wang JW, Ke JF, Zhang ZH, Lu JX, Li LX. Albuminuria but not low eGFR is closely associated with atherosclerosis in patients with type 2 diabetes: an observational study. Diabetol Metab Syndr 2022; 14:50. [PMID: 35413936 PMCID: PMC9006541 DOI: 10.1186/s13098-022-00824-x] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2021] [Accepted: 04/03/2022] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND There is still controversy regarding the associations of urinary albumin excretion (UAE) and estimated glomerular filtration rate (eGFR) with atherosclerosis in patients with type 2 diabetes mellitus (T2DM). Therefore, it is necessary to explore the correlation between them in T2DM patients. METHODS We conducted a survey involving 2565 T2DM patients from a single center. The study cohort was classified into three groups based on the levels of albuminuria: normal UAE (UAE < 30 mg/24 h), moderate UAE (UAE between 30 and 299 mg/24 h) and high UAE (UAE ≥ 300 mg/24 h). Additionally, the patients were divided into three separate groups according to eGFR levels, including low eGFR (eGFR < 60 ml/min/1.73 m2), intermediate eGFR (eGFR 60-89 ml/min/1.73 m2) and normal eGFR (eGFR ≥ 90 ml/min/1.73 m2) groups. Atherosclerotic lesions were compared among the three UAE and eGFR groups. Regression analyses were used to assess the associations of atherosclerotic lesions with UAE and eGFR in T2DM. RESULTS After controlling for age, sex and diabetes duration, the prevalence of atherosclerotic plaque and stenosis were significantly increased from the normal to high UAE groups (plaque: 72.2%, 78.6% and 87.3%, respectively, p = 0.016 for trend; stenosis: 14.0%, 25.5% and 37.3%, respectively, p < 0.001 for trend). Likewise, the values of carotid intima-media thickness (CIMT) and femoral intima-media thickness (FIMT) were also obviously increased from the normal to high UAE groups (CIMT: p < 0.001 for trend; FIMT: p = 0.001 for trend). Conversely, only the FIMT value was clearly increased from the low to normal eGFR groups (p = 0.001 for trend). Fully adjusted regression analyses revealed that UAE was closely associated with the presence of atherosclerotic plaque (OR 1.20, 95% CI 1.03-1.40, p = 0.020) and stenosis (OR 1.17, 95% CI 1.01-1.35, p = 0.036), and with the values of CIMT (β 0.05, 95% CI 0.01-0.10, p = 0.029) and FIMT (β 0.07, 95% CI 0.03-0.11, p = 0.001) in T2DM patients. However, there was no significant association between eGFR levels and atherosclerotic lesions in T2DM after adjustment for multiple confounding factors. CONCLUSIONS Overall, albuminuria rather than low eGFR is closely associated with atherosclerotic lesions in T2DM patients. Albuminuria is an independent risk factor for carotid and femoral atherosclerotic lesions in T2DM. Therefore, albuminuria may be a potential early marker to predict the development of atherosclerosis in patients with T2DM.
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Affiliation(s)
- Jun-Wei Wang
- Department of Endocrinology and Metabolism, Shanghai Clinical Center for Diabetes, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China
| | - Jiang-Feng Ke
- Department of Endocrinology and Metabolism, Shanghai Clinical Center for Diabetes, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China
| | - Zhi-Hui Zhang
- Department of Endocrinology and Metabolism, Shanghai Clinical Center for Diabetes, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China
| | - Jun-Xi Lu
- Department of Endocrinology and Metabolism, Shanghai Clinical Center for Diabetes, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China
| | - Lian-Xi Li
- Department of Endocrinology and Metabolism, Shanghai Clinical Center for Diabetes, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China.
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Gurung RL, Dorajoo R, M Y, Liu JJ, Pek SLT, Wang J, Wang L, Sim X, Liu S, Shao YM, Ang K, Subramaniam T, Tang WE, Sum CF, Liu JJ, Lim SC. Association of Genetic Variants for Plasma LRG1 With Rapid Decline in Kidney Function in Patients With Type 2 Diabetes. J Clin Endocrinol Metab 2021; 106:2384-2394. [PMID: 33889958 DOI: 10.1210/clinem/dgab268] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2021] [Indexed: 11/19/2022]
Abstract
CONTEXT Elevated levels of plasma leucine-rich α-2-glycoprotein 1 (LRG1), a component of transforming growth factor beta signaling, are associated with development and progression of chronic kidney disease in patients with type 2 diabetes (T2D). However, whether this relationship is causal is uncertain. OBJECTIVES To identify genetic variants associated with plasma LRG1 levels and determine whether genetically predicted plasma LRG1 contributes to a rapid decline in kidney function (RDKF) in patients with T2D. DESIGN AND PARTICIPANTS We performed a genome-wide association study of plasma LRG1 among 3694 T2D individuals [1881 (983 Chinese, 420 Malay, and 478 Indian) discovery from Singapore Study of Macro-angiopathy and Micro-vascular Reactivity in Type 2 Diabetes cohort and 1813 (Chinese) validation from Diabetic Nephropathy cohort]. One- sample Mendelian randomization analysis was performed among 1337 T2D Chinese participants with preserved glomerular filtration function [baseline estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2)]. RDKF was defined as an eGFR decline of 3 mL/min/1.73 m2/year or greater. RESULTS We identified rs4806985 variant near LRG1 locus robustly associated with plasma LRG1 levels (meta P = 6.66 × 10-16). Among 1337 participants, 344 (26%) developed RDKF, and the rs4806985 variant was associated with higher odds of RDKF (meta odds ratio = 1.23, P = 0.030 adjusted for age and sex). Mendelian randomization analysis provided evidence for a potential causal effect of plasma LRG1 on kidney function decline in T2D (P < 0.05). CONCLUSION We demonstrate that genetically influenced plasma LRG1 increases the risk of RDKF in T2D patients, suggesting plasma LRG1 as a potential treatment target. However, further studies are warranted to elucidate underlying pathways to provide insight into diabetic kidney disease prevention.
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Affiliation(s)
- Resham Lal Gurung
- Clinical Research Unit, Khoo Teck Puat Hospital, Singapore, Singapore
| | - Rajkumar Dorajoo
- Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore
- Health Services and Systems Research, Duke-NUS Medical School, Singapore, Singapore
| | - Yiamunaa M
- Clinical Research Unit, Khoo Teck Puat Hospital, Singapore, Singapore
| | - Jian-Jun Liu
- Clinical Research Unit, Khoo Teck Puat Hospital, Singapore, Singapore
| | | | - Jiexun Wang
- Clinical Research Unit, Khoo Teck Puat Hospital, Singapore, Singapore
| | - Ling Wang
- Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore
| | - Xueling Sim
- Saw Swee Hock School of Public Heath, Singapore, Singapore
| | - Sylvia Liu
- Clinical Research Unit, Khoo Teck Puat Hospital, Singapore, Singapore
| | - Yi-Ming Shao
- Clinical Research Unit, Khoo Teck Puat Hospital, Singapore, Singapore
| | - Keven Ang
- Clinical Research Unit, Khoo Teck Puat Hospital, Singapore, Singapore
| | | | - Wern Ee Tang
- National Healthcare Group Polyclinic, Singapore, Singapore
| | - Chee Fang Sum
- Diabetes Centre, Admiralty Medical Centre, Singapore, Singapore
| | - Jian-Jun Liu
- Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Su Chi Lim
- Clinical Research Unit, Khoo Teck Puat Hospital, Singapore, Singapore
- Saw Swee Hock School of Public Heath, Singapore, Singapore
- Diabetes Centre, Admiralty Medical Centre, Singapore, Singapore
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Lin SC, Wu TJ, Wu DA, Hsu BG. Hypoadiponectinemia is associated with aortic stiffness in nondialysis diabetic patients with stage 3-5 chronic kidney disease. Vascular 2021; 30:384-391. [PMID: 33866881 DOI: 10.1177/17085381211007602] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
OBJECTIVES Albuminuria and serum adiponectin levels are factors that have been associated with the development of cardiovascular disease in patients with diabetes mellitus. Here we investigated the relationship between serum adiponectin levels and aortic stiffness in nondialysis diabetic kidney disease patients with stage 3-5 chronic kidney disease. METHODS Fasting blood samples were obtained from 80 nondialysis diabetic kidney disease patients with stage 3-5 chronic kidney disease. Carotid-femoral pulse wave velocity (cfPWV) was measured using applanation tonometry; cfPWV values of >10 m/s were defined as aortic stiffness. Serum adiponectin levels were determined by enzyme immunoassay. RESULTS Forty-two patients (52.5%) with nondialysis diabetic kidney disease were diagnosed with aortic stiffness. The patients in this group were older (p = 0.011), had higher systolic blood pressure (p = 0.002) and urine albumin-to-creatinine ratios (p = 0.013), included fewer females (p = 0.024), and had lower serum adiponectin (p = 0.001) levels than those in the control group. Multivariable logistic regression analysis revealed that serum adiponectin was independently associated with aortic stiffness (odds ratio = 0.930, 95% confidence interval: 0.884-0.978, p = 0.005) and also positively correlated with cfPWV values by multivariable linear regression (β = -0.309, p = 0.002) in nondialysis diabetic kidney disease patients. CONCLUSIONS The results suggested that serum adiponectin levels could be used to predict aortic stiffness in nondialysis diabetic kidney disease patients with stage 3-5 chronic kidney disease.
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Affiliation(s)
- Ssu-Chin Lin
- Division of Nephrology, Department of Medicine, Hualien Armed Forces General Hospital, Hualien.,Department of Nursing, Hualien Armed Forces General Hospital, Hualien
| | - Tsung-Jui Wu
- Division of Nephrology, Department of Medicine, Hualien Armed Forces General Hospital, Hualien
| | - Du-An Wu
- Division of Metabolism and Endocrinology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien.,School of Medicine, Tzu Chi University, Hualien
| | - Bang-Gee Hsu
- School of Medicine, Tzu Chi University, Hualien.,Division of Nephrology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien
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Lim GJ, Liu YL, Low S, Ang K, Tavintharan S, Sum CF, Lim SC. Medical Costs Associated with Severity of Chronic Kidney Disease in Type 2
Diabetes Mellitus in Singapore. ANNALS OF THE ACADEMY OF MEDICINE, SINGAPORE 2020. [DOI: 10.47102/annals-acadmedsg.202032] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
Introduction: This was a retrospective cross-sectional study to assess the impact of
chronic kidney disease (CKD) and its severity in Type 2 diabetes mellitus (T2DM) on
direct medical costs, and the effects of economic burden on CKD related complications in
T2DM in Singapore.
Methods: A total of 1,275 T2DM patients were recruited by the diabetes centre at
Khoo Teck Puat Hospital from 2011–2014. CKD stages were classified based on improving
global outcome (KDIGO) categories, namely the estimated glomerular filtration rate
(eGFR) and albuminuria kidney disease. Medical costs were extracted from the hospital
administrative database.
Results: CKD occurred in 57.3% of patients. The total mean cost ratio for CKD relative
to non-CKD was 2.2 (P<0.001). Mean (median) baseline annual unadjusted costs were
significantly higher with increasing CKD severity—S$1,523 (S$949), S$2,065 (S$1,198),
S$3,502 (S$1,613), and S$5,328 (S$2,556) for low, moderate, high, and very high risk
respectively (P<0.001). CKD (P<0.001), age at study entry (P=0.001), Malay ethnicity
(P=0.035), duration of diabetes mellitus (DM; P<0.001), use of statins/fibrates (P=0.021),
and modified Diabetes Complications Severity Index (DCSI) (P<0.001) were positively
associated with mean annual direct medical costs in the univariate analysis. In the fully
adjusted model, association with mean annual total costs persisted for CKD, CKD
severity and modified DCSI.
Conclusion: The presence and increased severity of CKD is significantly associated
with higher direct medical costs in T2DM patients. Actively preventing the occurrence
and progression in DM-induced CKD may significantly reduce healthcare resource
consumption and healthcare costs.
Keywords: Chronic kidney disease, costs, endocrinology, nephrology
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Ye C, Gong J, Wang T, Luo L, Lian G, Wang H, Chen W, Xie L. Relationship between high-normal albuminuria and arterial stiffness in Chinese population. J Clin Hypertens (Greenwich) 2020; 22:1674-1681. [PMID: 33284512 DOI: 10.1111/jch.13979] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2020] [Revised: 06/15/2020] [Accepted: 07/01/2020] [Indexed: 12/23/2022]
Abstract
High-normal albuminuria is related to the morbidity and mortality of cardiovascular disease. Arterial stiffness has been regarded as a predictor of cardiovascular disease. However, the relationship between high-normal albuminuria and arterial stiffness is uncertain in Chinese population. A total of 1343 Chinese participants (aged 58.9 ± 12.1 years, 63.53% male) were included in this study. High-normal albuminuria was defined as urinary albumin-to-creatinine ratio (UACR) above the median within normal albuminuria. Based on the level of UACR, all participants were divided into low-normal albuminuria group (UACR < 6.36 mg/g, n = 580), high-normal albuminuria group (6.36 mg/g ≤ UACR < 30 mg/g, n = 581), microalbuminuria (30 mg/g ≤ UACR < 300 mg/g, n = 162), and macroalbuminuria (UACR ≥ 300 mg/g, n = 20). Arterial stiffness was assessed by measuring carotid-femoral pulse wave velocity (cfPWV). With the increment of UACR, the level of cfPWV was increased gradually (P < .001). Stepwise multiple regression analysis showed that systolic blood pressure, age, serum creatinine, heart rate, logarithmic (LG)-transformed UACR, and fasting plasma glucose were independently associated with cfPWV in all subjects (P < .001). LG-UACR was found to be related to cfPWV in high-normal albuminuria and macroalbuminuria subjects. After further stratification in the high-normal albuminuria subjects, their relation remained in male, elderly over 65 years old, or normotensives. In summary, UACR is associated with arterial stiffness in subjects with proteinuria excretion in high normal level. High-normal albuminuria might be an early indicator of arterial stiffness, especially in male, elderly, or normotensives in Chinese population. Furthermore, age and blood pressure are still observed to be the most important risk factor of arterial stiffness.
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Affiliation(s)
- Chaoyi Ye
- Department of Geriatrics, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.,Fujian Hypertension Research Institute, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Jin Gong
- Department of Geriatrics, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.,Fujian Hypertension Research Institute, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.,Department of General Medicine, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Tingjun Wang
- Department of Geriatrics, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.,Department of General Medicine, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Li Luo
- Department of Geriatrics, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.,Fujian Hypertension Research Institute, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.,Department of General Medicine, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Guili Lian
- Fujian Hypertension Research Institute, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Huajun Wang
- Fujian Hypertension Research Institute, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Weixiao Chen
- Department of Geriatrics, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.,Fujian Hypertension Research Institute, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Liangdi Xie
- Department of Geriatrics, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.,Fujian Hypertension Research Institute, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.,Department of General Medicine, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
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Patoulias D, Papadopoulos C, Stavropoulos K, Zografou I, Doumas M, Karagiannis A. Prognostic value of arterial stiffness measurements in cardiovascular disease, diabetes, and its complications: The potential role of sodium-glucose co-transporter-2 inhibitors. J Clin Hypertens (Greenwich) 2020; 22:562-571. [PMID: 32058679 PMCID: PMC8029715 DOI: 10.1111/jch.13831] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2019] [Revised: 12/02/2019] [Accepted: 12/10/2019] [Indexed: 12/12/2022]
Abstract
Type 2 diabetes mellitus (T2DM) constitutes a global pandemic, representing the 7th cause of death worldwide. Morbidity and mortality of patients with T2DM are gradually increasing, while prevalence of cardiovascular disease (CVD) among these patients is almost 14% greater compared to the general population. Arterial stiffness is nowadays a valuable biomarker of CVD and a promising treatment target in specific patient groups, including those suffering from T2DM. Despite that fact, design of the available studies cannot prove causal relationship. Recently, a new antidiabetic drug class, namely sodium-glucose co-transporter-2 (SGLT-2) inhibitors, has attracted scientific interest, due to their multiple, beneficial, pleiotropic effects, especially those focused on CVD. There is limited relevant literature concerning the effects of SGLT-2 inhibitors on arterial stiffness, while retrieved results might be considered as conflicting. The aim of the present review article is to summarize acquired knowledge regarding the prognostic role of arterial stiffness in T2DM, along with the presentation of retrieved data on the potential role of SGLT-2 inhibitors.
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Affiliation(s)
- Dimitrios Patoulias
- Second Propedeutic Department of Internal MedicineGeneral Hospital “Hippokration”Aristotle University of ThessalonikiThessalonikiGreece
| | - Christodoulos Papadopoulos
- Third Department of CardiologyGeneral Hospital “Hippokration”Aristotle University of ThessalonikiThessalonikiGreece
| | - Konstantinos Stavropoulos
- Second Propedeutic Department of Internal MedicineGeneral Hospital “Hippokration”Aristotle University of ThessalonikiThessalonikiGreece
| | - Ioanna Zografou
- Second Propedeutic Department of Internal MedicineGeneral Hospital “Hippokration”Aristotle University of ThessalonikiThessalonikiGreece
| | - Michael Doumas
- Second Propedeutic Department of Internal MedicineGeneral Hospital “Hippokration”Aristotle University of ThessalonikiThessalonikiGreece
- Veterans Affair Medical CenterGeorge Washington UniversityWashingtonDCUSA
| | - Asterios Karagiannis
- Second Propedeutic Department of Internal MedicineGeneral Hospital “Hippokration”Aristotle University of ThessalonikiThessalonikiGreece
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Zhang X, Pek SLT, Tavintharan S, Sum CF, Lim SC, Ang K, Yeo D, Ee TW, Yip CC, Kumari N. Leucine-rich α-2-glycoprotein predicts proliferative diabetic retinopathy in type 2 diabetes. J Diabetes Complications 2019; 33:651-656. [PMID: 31256924 DOI: 10.1016/j.jdiacomp.2019.05.021] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2018] [Revised: 05/08/2019] [Accepted: 05/26/2019] [Indexed: 12/17/2022]
Abstract
AIM We aim to examine the association of plasma leucine-rich-α-2-glycoprotein 1 (LRG1) with diabetic retinopathy (DR) in type 2 diabetes. METHODS At baseline visit, plasma LRG1 levels were assessed using ELISA. Central arterial stiffness was estimated by carotid-femoral pulse wave velocity (PWV). At follow-up visit (median = 3.2 years), digital color fundus photographs were assessed for DR. DR severity was categorized into non-proliferative DR (NPDR) and proliferative DR (PDR). RESULTS DR was diagnosed in 396 (32.8%) of 1206 patients. DR has higher LRG1 than non-DR (19.5 ± 11.3vs.16.9 ± 8.9 μg/ml, p ≪ 0.001). After adjustment, LRG1 was not associated with DR (OR = 1.2, [95% CI, 0.96-1.30], p = 0.16). LRG1 was higher in PDR (n = 107) than NPDR (n = 270) (23.2 ± 15.4vs.18.1 ± 8.9 μg/ml, n = 270, p ≪ 0.001). After adjustment, with 1-SD increase in LRG1, the relative risk of NPDR and PDR was 0.99 ([0.83-1.18], p = 0.91) and 1.42 ([95% CI, 1.14-1.76], p = 0.002) (p-trend = 0.01), respectively. We didn't observe significant improvement in AUC after adding LRG1 into the model. Baseline PWV mediated 12.0% of the association between LRG1 and PDR (p = 0.03). CONCLUSION Baseline plasma LRG1 is associated with PDR, suggesting it maybe a promising biomarker for prediction for advanced proliferative stages of DR. The mediation result indicates the potential benefit of ameliorating central arterial stiffness to prevent PDR.
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Affiliation(s)
- Xiao Zhang
- Clinical Research Unit, Khoo Teck Puat Hospital, Singapore
| | - Sharon L T Pek
- Clinical Research Unit, Khoo Teck Puat Hospital, Singapore
| | - Subramaniam Tavintharan
- Diabetes Centre, Khoo Teck Puat Hospital, Singapore; Department of Medicine, Khoo Teck Puat Hospital, Singapore
| | - Chee Fang Sum
- Diabetes Centre, Khoo Teck Puat Hospital, Singapore; Department of Medicine, Khoo Teck Puat Hospital, Singapore
| | - Su Chi Lim
- Diabetes Centre, Khoo Teck Puat Hospital, Singapore; Department of Medicine, Khoo Teck Puat Hospital, Singapore; Saw Swee Hock School of Public Health, National University of Singapore, Singapore
| | - Keven Ang
- Clinical Research Unit, Khoo Teck Puat Hospital, Singapore
| | - Darren Yeo
- Clinical Research Unit, Khoo Teck Puat Hospital, Singapore
| | - Tang Wern Ee
- National Healthcare Group Polyclinics, Singapore
| | - Chee Chew Yip
- Department of ophthalmology and Visual Sciences, Khoo Teck Puat Hospital, Singapore
| | - Neelam Kumari
- Department of ophthalmology and Visual Sciences, Khoo Teck Puat Hospital, Singapore.
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Moh MC, Sum CF, Tavintharan S, Ang K, Kwan PY, Lee SBM, Tang WE, Lim SC. Gain in adiposity over 3 years is associated with progressive renal decline in multi-ethnic South-east Asians with type 2 diabetes. J Diabetes 2019; 11:316-325. [PMID: 30178527 DOI: 10.1111/1753-0407.12848] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2017] [Revised: 08/23/2018] [Accepted: 08/29/2018] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND This study evaluated the association between gain in adiposity and renal decline in a large prospective multiethnic South-east Asian cohort with type 2 diabetes mellitus (T2DM). METHODS Three years after the baseline visit, 2057 T2DM subjects were recalled for reassessment. The final cohort comprised 1014 subjects and was categorized into tertiles based on changes in body weight (ΔWt), body mass index (ΔBMI), visceral fat area (ΔVFA), and BMI-adjusted VFA (ΔVFABMI ). Outcomes included annual and rapid (≥3 mL/min per 1.73 m2 per year) decline in estimated glomerular filtration rate (eGFR) and progression of albuminuria. RESULTS Participants (mean [±SD] age 57 ± 11 years, 48.8% women, BMI 27.7 ± 5.4 kg/m2 ) exhibited a median annual decline in eGFR of 1.0 mL/min per 1.73 m2 . Compared with the lower tertiles, Tertile 3 of ΔWt, ΔBMI, ΔVFA, and ΔVFABMI had the highest anthropometric increase, albeit of modest magnitude, and this was accompanied by the worst renal outcomes (all P < 0.05). The relationship between annual eGFR decline and Tertile 3 of ΔWt, ΔBMI, and ΔVFABMI persisted after multivariate adjustment in men but not in women. In addition, Tertile 3 of ΔWt, ΔBMI, ΔVFA, and ΔVFABMI predicted rapid eGFR decline. Anthropometric gains were also associated with progression of albuminuria. CONCLUSIONS Modest longitudinal gain in adiposity was associated with progressive renal decline in T2DM patients, suggesting that increased adiposity over time adversely affects renal outcomes. Therefore, a carefully designed weight-neutral or -loss antidiabetic treatment regimen is important when managing T2DM in the clinic.
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Affiliation(s)
- Mei Chung Moh
- Clinical Research Unit, Khoo Teck Puat Hospital, Singapore
| | - Chee Fang Sum
- Diabetes Centre, Admiralty Medical Centre, Khoo Teck Puat Hospital, Singapore
| | - Subramaniam Tavintharan
- Clinical Research Unit, Khoo Teck Puat Hospital, Singapore
- Diabetes Centre, Admiralty Medical Centre, Khoo Teck Puat Hospital, Singapore
| | - Keven Ang
- Clinical Research Unit, Khoo Teck Puat Hospital, Singapore
| | - Pek Yee Kwan
- National Healthcare Group Polyclinics, Singapore
| | | | - Wern Ee Tang
- National Healthcare Group Polyclinics, Singapore
| | - Su Chi Lim
- Clinical Research Unit, Khoo Teck Puat Hospital, Singapore
- Diabetes Centre, Admiralty Medical Centre, Khoo Teck Puat Hospital, Singapore
- Saw Swee Hock School of Public Health, National University Hospital, Singapore
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Zhang X, Kumari N, Low S, Ang K, Yeo D, Yeoh LY, Liu A, Kwan PY, Tang WE, Tavintharan S, Sum CF, Lim SC. The association of serum creatinine and estimated glomerular filtration rate variability with diabetic retinopathy in Asians with type 2 diabetes: A nested case-control study. Diab Vasc Dis Res 2018; 15:548-558. [PMID: 30014713 DOI: 10.1177/1479164118786969] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/07/2023] Open
Abstract
BACKGROUND Fluctuation of kidney function may signify intra-glomerular microvascular hemodynamic instability. We aim to examine the association of long-term serum creatinine and estimated glomerular filtration rate variability with diabetic retinopathy. METHODS We included type 2 diabetes mellitus patients who attended the Diabetes Centre in 2011-2014 and were followed up (median = 3.2 years). Digital colour fundus photographs were assessed for diabetic retinopathy at follow-up. Diabetic retinopathy severity was categorized into non-proliferative diabetic retinopathy and proliferative diabetic retinopathy. We conducted a nested case-control study involving 177 diabetic retinopathy (118 non-proliferative diabetic retinopathy, 50 proliferative diabetic retinopathy) and 327 age- and gender-matched non-diabetic retinopathy. Serum creatinine measured before follow-up visit was obtained (⩾3 readings/patient). Variability was calculated as intra-individual standard deviation/√ n/( n - 1). RESULTS Diabetic retinopathy have higher adjusted-serum creatinine-standard deviation than non-diabetic retinopathy [9.1 (4.9-21.6) vs 5.4 (3.4-10.1) µM, p < 0.001]. After multivariable adjustment, adjusted-serum creatinine-standard deviation was associated with diabetic retinopathy [odds ratio = 1.47, 95% confidence interval (1.02-2.10), p = 0.04]. The area under the curve increased significantly after adding adjusted-serum creatinine-standard deviation [0.70 (0.65-0.75) vs 0.72 (0.68-0.77), p < 0.03]. Proliferative diabetic retinopathy have higher adjusted-serum creatinine-standard deviation than non-proliferative diabetic retinopathy [15.5 (6.6-39.7) vs 7.47 (4.52-17.8) µM, p < 0.001]. After adjustment, adjusted-serum creatinine-standard deviation remained associated with non-proliferative diabetic retinopathy [1.48 (1.04-2.12), p = 0.03] and proliferative diabetic retinopathy [2.43 (1.34-4.39), p = 0.003; p-trend = 0.002]. Similar findings were observed for estimated glomerular filtration rate variability. CONCLUSION Serum creatinine and estimated glomerular filtration rate variability is associated with the presence and severity of diabetic retinopathy independent of intra-individual means. This may inform novel therapeutic strategies aiming to achieve stable renal function in type 2 diabetes mellitus.
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Affiliation(s)
- Xiao Zhang
- 1 Clinical Research Unit, Khoo Teck Puat Hospital, Singapore
| | - Neelam Kumari
- 2 Department of ophthalmology and Visual Sciences, Khoo Teck Puat Hospital, Singapore
| | - Serena Low
- 1 Clinical Research Unit, Khoo Teck Puat Hospital, Singapore
| | - Keven Ang
- 1 Clinical Research Unit, Khoo Teck Puat Hospital, Singapore
| | - Darren Yeo
- 1 Clinical Research Unit, Khoo Teck Puat Hospital, Singapore
| | - Lee Ying Yeoh
- 3 Department of Medicine, Khoo Teck Puat Hospital, Singapore
| | - Allen Liu
- 3 Department of Medicine, Khoo Teck Puat Hospital, Singapore
| | - Pek Yee Kwan
- 4 National Healthcare Group Polyclinics, Singapore
| | - Wern Ee Tang
- 4 National Healthcare Group Polyclinics, Singapore
| | - Subramaniam Tavintharan
- 3 Department of Medicine, Khoo Teck Puat Hospital, Singapore
- 5 Diabetes Centre, Khoo Teck Puat Hospital, Singapore
| | - Chee Fang Sum
- 3 Department of Medicine, Khoo Teck Puat Hospital, Singapore
- 5 Diabetes Centre, Khoo Teck Puat Hospital, Singapore
| | - Su Chi Lim
- 3 Department of Medicine, Khoo Teck Puat Hospital, Singapore
- 5 Diabetes Centre, Khoo Teck Puat Hospital, Singapore
- 6 Saw Swee Hock School of Public Health, National University of Singapore, Singapore
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Pulsatile interaction between the macro-vasculature and micro-vasculature: proof-of-concept among patients with type 2 diabetes. Eur J Appl Physiol 2018; 118:2455-2463. [DOI: 10.1007/s00421-018-3972-2] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2018] [Accepted: 08/21/2018] [Indexed: 10/28/2022]
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Moh A, Neelam K, Zhang X, Sum CF, Tavintharan S, Ang K, Lee SBM, Tang WE, Lim SC. Excess visceral adiposity is associated with diabetic retinopathy in a multiethnic Asian cohort with longstanding type 2 diabetes. Endocr Res 2018; 43:186-194. [PMID: 29624091 DOI: 10.1080/07435800.2018.1451541] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/17/2022]
Abstract
UNLABELLED Purpose/Aim: Diabetic retinopathy (DR) is the most common diabetic microvascular complication, and it typically develops after 10 years of diabetes diagnosis. The primary aim of this study was to evaluate the association between adiposity and DR susceptibility among individuals with longstanding type 2 diabetes mellitus (T2D). MATERIALS AND METHODS In this cross-sectional study, DR was assessed by fundus photography in 953 T2D subjects. DR prevalence by categories of T2D duration was evaluated. In a sub-cohort analysis, subjects having T2D for ≥10 years were divided into DR (N = 241) and non-DR (N = 377) groups. Measures of adiposity including body mass index (BMI), waist circumference (WC), and visceral fat area (VFA) were analyzed. Urinary albumin:creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR) were measured. RESULTS DR prevalence markedly increased 10 years after T2D diagnosis (p < 0.001). Among subjects with T2D duration ≥10 years, BMI, WC, and VFA were elevated in DR compared with non-DR (all p < 0.05). Contrasting with BMI and WC, the association between VFA and DR sustained adjustment for demographics, metabolic factors, and insulin treatment (OR: 1.060, 95% CI: 1.004-1.119, p = 0.035). However, the association became insignificant after controlling for ACR and eGFR. Mediation analysis revealed that ACR and eGFR explained 47.3% of the relationship between VFA and DR. CONCLUSIONS The findings suggest that visceral adiposity is associated with DR in individuals with longstanding T2D. This relationship may be attributable to generalized vascular injury as reflected by coexisting renal burden. Therefore, effective management of visceral adiposity and ameliorating renal burden may ameliorate susceptibility to DR.
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Affiliation(s)
- Angela Moh
- a Clinical Research Unit , Khoo Teck Puat Hospital , Singapore
| | - Kumari Neelam
- b Ophthalmology and Visual Sciences , Khoo Teck Puat Hospital , Singapore
| | - Xiao Zhang
- a Clinical Research Unit , Khoo Teck Puat Hospital , Singapore
| | - Chee Fang Sum
- c Diabetes Centre, Admiralty Medical Centre , Khoo Teck Puat Hospital , Singapore
| | - Subramaniam Tavintharan
- a Clinical Research Unit , Khoo Teck Puat Hospital , Singapore
- c Diabetes Centre, Admiralty Medical Centre , Khoo Teck Puat Hospital , Singapore
| | - Keven Ang
- a Clinical Research Unit , Khoo Teck Puat Hospital , Singapore
| | | | - Wern Ee Tang
- d National Healthcare Group Polyclinics , Singapore
| | - Su Chi Lim
- a Clinical Research Unit , Khoo Teck Puat Hospital , Singapore
- c Diabetes Centre, Admiralty Medical Centre , Khoo Teck Puat Hospital , Singapore
- e Saw Swee Hock School of Public Health, National University Hospital , Singapore
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Zhang X, Low S, Ang K, Yeoh LY, Tavintharan S, Sum CF, Lim SC. Microvascular endothelial function is an independent predictor for albuminuria progression among Asians with type 2 diabetes-A prospective cohort study. Microcirculation 2018; 25:e12453. [PMID: 29602193 DOI: 10.1111/micc.12453] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2017] [Accepted: 03/21/2018] [Indexed: 11/30/2022]
Abstract
OBJECTIVE We aim to investigate whether microvascular endothelial dysfunction is an independent predictor for future albuminuria progression in T2DM cohort. METHODS A total of 1098 patients with T2DM were clinically assessed at baseline and 3.2-year follow-up. Progression was defined as transition from normoalbuminuria (ACR <30 mg/g) to microalbuminuria (ACR = 30-299 mg/g) or macroalbuminuria (ACR >300 mg/g), or microalbuminuria to macroalbuminuria. Microvascular endothelial vasodilation at baseline was quantified using LDF. The increase in perfusion in response to ACh and NaNP was calculated. Logistic regression model was used to estimate the OR for albuminuria progression. RESULTS Albuminuria progression occurred in 226 (20.6%) patients. Baseline ACh was significantly higher in nonprogression than progression group (80.0 ± 53.2% vs 72.0 ± 49.7%, P = .04). There is no significant difference in NaNP between the two groups (111.1 ± 80.3% vs 121.1 ± 87.4%, P = .12). After multivariable adjustment, 1-SD increase in ACh was marginally associated with albuminuria progression (OR = 0.87, 95% CI, 0.72-1.02, P = .08) in all patients. When stratified by baseline albuminuria, 1-SD increase in ACh was significantly associated with albuminuria progression in normoalbuminuria (OR = 0.76, 95% CI, 0.59-0.97, P = .03), but not in microalbuminuria patients (OR = 1.18, 95% CI, 0.81-1.70, P = .39). CONCLUSIONS Impaired endothelial-dependent microvascular reactivity predicts the onset of albuminuria progression among T2DM patients with normoalbuminuria.
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Affiliation(s)
- Xiao Zhang
- Clinical Research Unit, Khoo Teck Puat Hospital, Singapore, Singapore
| | - Serena Low
- Clinical Research Unit, Khoo Teck Puat Hospital, Singapore, Singapore
| | - Keven Ang
- Clinical Research Unit, Khoo Teck Puat Hospital, Singapore, Singapore
| | - Lee Ying Yeoh
- Department of Medicine, Khoo Teck Puat Hospital, Singapore, Singapore
| | - Subramaniam Tavintharan
- Department of Medicine, Khoo Teck Puat Hospital, Singapore, Singapore.,Diabetes Centre, Khoo Teck Puat Hospital, Singapore, Singapore
| | - Chee Fang Sum
- Department of Medicine, Khoo Teck Puat Hospital, Singapore, Singapore.,Diabetes Centre, Khoo Teck Puat Hospital, Singapore, Singapore
| | - Su Chi Lim
- Department of Medicine, Khoo Teck Puat Hospital, Singapore, Singapore.,Diabetes Centre, Khoo Teck Puat Hospital, Singapore, Singapore.,Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore
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Lim SC, Dorajoo R, Zhang X, Wang L, Ang SF, Tan CSH, Yeoh LY, Ng XW, Li N, Su C, Liu S, Wong MDS, Low KMS, Yao AO, Babitha J, Fun S, Zhou S, Lee SBM, Tang WE, Tavintharan S, Sum CF, Liu JJ. Genetic variants in the receptor for advanced glycation end products (RAGE) gene were associated with circulating soluble RAGE level but not with renal function among Asians with type 2 diabetes: a genome-wide association study. Nephrol Dial Transplant 2018; 32:1697-1704. [PMID: 27448675 DOI: 10.1093/ndt/gfw263] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2016] [Accepted: 05/30/2016] [Indexed: 01/26/2023] Open
Abstract
Background The soluble receptor for advanced glycation end products (sRAGE) has been shown to play an important role in diabetic complications. We conducted genome-wide association study (GWAS) of sRAGE in Asian type 2 diabetes mellitus (T2DM) patient and validated the association in an independent cohort of T2DM. Methods GWAS for sRAGE was performed in 2058 T2DM patients. Associations between single-nucleotide polymorphisms (SNPs) and plasma sRAGE level were analyzed in an additive model using a linear mixed model. To validate the associations, we performed de novo genotyping in an independent cohort (n = 1984). We selected the top SNP for assessment with diabetic kidney disease (DKD). Results The strongest SNP, rs2070600C>T (P = 1.21 × 10-52), was a genotyped, missense SNP located on chromosome 6, corresponding to the RAGE (AGER) gene locus, the gene encoding RAGE. Conditioning analysis on rs2070600 revealed that rs2071288C>T was the top genotyped independent SNP (P = 8.36 × 10-10). Both SNPs were strongly and dose-dependently correlated with sRAGE level (TT = 399.6 pg/mL, CT = 737.0 pg/mL and CC = 967.0 pg/mL, P < 0.001 for rs2070600; TT = 687.9 pg/mL, CT = 737.6 pg/mL and CC = 904.7 pg/mL, P < 0.001 for rs2072188). Both SNPs were robustly replicated in the independent cohort, especially among Chinese patients (P = 9.02 × 10-72 for rs2070600; P = 1.13 × 10-9 for rs2071288). Log-transformed sRAGE was associated with DKD after adjustment for age, gender and ethnicity in pooled cohorts [odds ratio 2.536 (95% confidence interval 1.864-3.450), P < 0.001]. However, we did not observe any significant association between rs2070600 and DKD. Conclusions Common variants in RAGE are strongly associated with plasma sRAGE level, which is associated with DKD. However, we did not find a causal link between sRAGE and renal function by Mendelian randomization.
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Affiliation(s)
- Su Chi Lim
- Diabetes Centre, Khoo Teck Puat Hospital, Singapore.,Department of Medicine, Khoo Teck Puat Hospital, Singapore
| | - Rajkumar Dorajoo
- Human Genetics, Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore
| | - Xiao Zhang
- Clinical Research Unit, Khoo Teck Puat Hospital, Singapore
| | - Ling Wang
- Human Genetics, Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore
| | - Su Fen Ang
- Clinical Research Unit, Khoo Teck Puat Hospital, Singapore
| | | | - Lee Ying Yeoh
- Department of Medicine, Khoo Teck Puat Hospital, Singapore
| | - Xiao Wei Ng
- Clinical Research Unit, Khoo Teck Puat Hospital, Singapore
| | - Na Li
- Clinical Research Unit, Khoo Teck Puat Hospital, Singapore
| | - Chang Su
- Clinical Research Unit, Khoo Teck Puat Hospital, Singapore
| | - Sylvia Liu
- Clinical Research Unit, Khoo Teck Puat Hospital, Singapore
| | | | | | - Amy Ou Yao
- Clinical Research Unit, Khoo Teck Puat Hospital, Singapore
| | | | - Sharon Fun
- Diabetes Centre, Khoo Teck Puat Hospital, Singapore
| | - Shiyi Zhou
- Clinical Research Unit, Khoo Teck Puat Hospital, Singapore
| | | | - Wern Ee Tang
- National Healthcare Group Polyclinics, Singapore
| | - Subramaniam Tavintharan
- Diabetes Centre, Khoo Teck Puat Hospital, Singapore.,Department of Medicine, Khoo Teck Puat Hospital, Singapore
| | - Chee Fang Sum
- Diabetes Centre, Khoo Teck Puat Hospital, Singapore.,Department of Medicine, Khoo Teck Puat Hospital, Singapore
| | - Jian-Jun Liu
- Human Genetics, Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore
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Cardoso CRL, Leite NC, Salles GC, Ferreira MT, Salles GF. Aortic stiffness and ambulatory blood pressure as predictors of diabetic kidney disease: a competing risks analysis from the Rio de Janeiro Type 2 Diabetes Cohort Study. Diabetologia 2018; 61:455-465. [PMID: 29063128 DOI: 10.1007/s00125-017-4484-z] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2017] [Accepted: 09/28/2017] [Indexed: 12/31/2022]
Abstract
AIMS/HYPOTHESIS Diabetic kidney disease (DKD) is a microvascular complication associated with poor control of blood glucose and BP. We aimed to evaluate the predictors of development and progression of DKD in a cohort of high-risk individuals with type 2 diabetes, placing emphasis on ambulatory BP and arterial stiffness. METHODS In a prospective study, 629 individuals without advanced renal failure had their renal function evaluated annually over a median follow-up period of 7.8 years. Ambulatory BP was monitored and aortic stiffness was assessed by carotid-femoral pulse wave velocity at baseline. Multivariate competing risks analysis with all-cause mortality, using the Fine and Gray approach, was used to examine the independent predictors of development and progression of DKD, a composite of development or progression of abnormal albuminuria and worsening of renal function (doubling of serum creatinine or progression to end-stage renal disease). RESULTS At baseline, 197 individuals had DKD. During follow-up, DKD developed or progressed in 195 individuals, abnormal albuminuria developed or progressed in 125 individuals and renal function deteriorated in 91. After adjustments for baseline albuminuria and renal function, age, sex, diabetes duration and use of renin-angiotensin antagonists, poorer control of blood glucose (HR 1.17; 95% CI 0.98, 1.40; p = 0.09 for each 1 SD increment in mean first-year HbA1c), higher ambulatory systolic BP (HR 1.28; 95% CI 1.09, 1.50; p = 0.003, for each 1 SD increase in daytime systolic BP [SBP]) and increased aortic stiffness (HR 1.16; 95% CI 1.00, 1.34; p = 0.05) were independent predictors of development or progression of DKD. At baseline, ambulatory BP was a stronger predictor than BP measured in the clinic. Aortic stiffness predicted abnormal albuminuria development or progression (HR 1.26; 95% CI 1.02, 1.56; p = 0.036) whereas ambulatory BP was a stronger predictor of renal function deterioration (HR 1.32; 95% CI 1.09, 1.60; p = 0.005 for daytime SBP). CONCLUSIONS/INTERPRETATION Poor blood glucose and BP control and increased aortic stiffness were the main predictors of development or progression of DKD; ambulatory SBP was a better predictor than BP measured in the clinic. Ambulatory BP monitoring and assessment of aortic stiffness should be more widely used in clinical type 2 diabetes management.
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Affiliation(s)
- Claudia R L Cardoso
- Department of Internal Medicine, University Hospital Clementino Fraga Filho, School of Medicine, Universidade Federal do Rio de Janeiro, Rua Rodolpho Paulo Rocco, 255, Cidade Universitária, Rio de Janeiro, CEP: 21941-913, Brazil
| | - Nathalie C Leite
- Department of Internal Medicine, University Hospital Clementino Fraga Filho, School of Medicine, Universidade Federal do Rio de Janeiro, Rua Rodolpho Paulo Rocco, 255, Cidade Universitária, Rio de Janeiro, CEP: 21941-913, Brazil
| | - Guilherme C Salles
- Civil Engineering Program, COPPE, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Marcel T Ferreira
- Department of Internal Medicine, University Hospital Clementino Fraga Filho, School of Medicine, Universidade Federal do Rio de Janeiro, Rua Rodolpho Paulo Rocco, 255, Cidade Universitária, Rio de Janeiro, CEP: 21941-913, Brazil
| | - Gil F Salles
- Department of Internal Medicine, University Hospital Clementino Fraga Filho, School of Medicine, Universidade Federal do Rio de Janeiro, Rua Rodolpho Paulo Rocco, 255, Cidade Universitária, Rio de Janeiro, CEP: 21941-913, Brazil.
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Gurung RL, M Y, Liu S, Liu JJ, Lim SC. Short Leukocyte Telomere Length Predicts Albuminuria Progression in Individuals With Type 2 Diabetes. Kidney Int Rep 2017; 3:592-601. [PMID: 29854966 PMCID: PMC5976822 DOI: 10.1016/j.ekir.2017.12.005] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2017] [Revised: 12/08/2017] [Accepted: 12/11/2017] [Indexed: 12/19/2022] Open
Abstract
Introduction Telomere length, a marker for biological aging, is implicated with diabetic kidney disease (DKD); however, the association between telomere length and albuminuria progression among Asian patients with type 2 diabetes (T2D) is not well understood. Here, we aim to study whether leukocyte telomere length (LTL) may independently predict albuminuria progression in patients with T2D with preserved renal filtration function (estimated GFR >60 ml/min per 1.73 m2 and urine albumin-to-creatinine ratio [uACR] <300 mg/g). Methods The baseline LTL was measured by real-time polymerase chain reaction in the SMART2D cohort (n = 691) with a median follow-up of 3 years. Albuminuria progression was defined as a change in albuminuria category to a higher category and at least 30% increase in uACR from baseline in 3 years. Results Progressors (n = 123) had significantly shorter median LTL compared with nonprogressors (n = 568) (0.58 [0.38–0.79] vs. 0.62 [0.45–0.88], P = 0.039). Compared with subjects with longer LTL (fourth quartile), subjects with shorter LTL (first quartile) had 1.93-fold (1.04–3.60, P = 0.038) increased risk for albuminuria progression after adjustment for traditional risk factors. The association of LTL with microalbuminuria to macroalbuminuria progression was stronger than its association with normoalbuminuria to microalbuminuria (odds ratio [OR]: 1.54; 95% confidence interval [CI]: 1.02–2.32; P = 0.042 vs. OR: 1.13; 95% CI: 0.91–1.40; P = 0.263 per 1-SD decrement in natural log-transformed LTL). Conclusion Therefore, our results demonstrated that in patients with T2D with preserved renal filtration function, LTL predicts albuminuria progression beyond traditional risk factors, suggesting LTL may be novel biomarker for DKD progression.
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Affiliation(s)
| | - Yiamunaa M
- Clinical Research Unit, Khoo Teck Puat Hospital, Singapore
| | - Sylvia Liu
- Clinical Research Unit, Khoo Teck Puat Hospital, Singapore
| | - Jian-Jun Liu
- Clinical Research Unit, Khoo Teck Puat Hospital, Singapore
| | - Su Chi Lim
- Clinical Research Unit, Khoo Teck Puat Hospital, Singapore
- Diabetes Centre, Khoo Teck Puat Hospital, Singapore
- Correspondence: Su Chi Lim, Clinical Research Unit, Khoo Teck Puat Hospital, 90 Yishun Central, Republic of Singapore 768828.
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18
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Liu JJ, Pek SLT, Ang K, Tavintharan S, Lim SC. Plasma Leucine-Rich α-2-Glycoprotein 1 Predicts Rapid eGFR Decline and Albuminuria Progression in Type 2 Diabetes Mellitus. J Clin Endocrinol Metab 2017; 102:3683-3691. [PMID: 28973352 DOI: 10.1210/jc.2017-00930] [Citation(s) in RCA: 49] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2017] [Accepted: 06/27/2017] [Indexed: 12/19/2022]
Abstract
CONTEXT Abnormal angiogenesis plays an important role in pathogenesis of diabetic kidney disease (DKD). Leucine-rich α-2 glycoprotein 1 (LRG1) is a newly identified angiogenic factor. OBJECTIVE To study whether plasma LRG1 may independently predict progression of DKD in individuals with type 2 diabetes mellitus (T2DM). DESIGN AND SETTING Prospective cohort study in a regional hospital. PATIENTS In total, 1226 T2DM participants were followed for a mean ± standard deviation (SD) of 3.1 ± 0.4 years. MAIN OUTCOMES Albuminuria progression was defined as elevation in albuminuria level to a higher category. Chronic kidney disease (CKD) progression [rapid estimated glomerular filtration rate (eGFR) decline] was defined as a 40% or greater deterioration in eGFR in 3 years. RESULTS Both participants with albuminuria progression and those with CKD progression had higher plasma LRG1 levels at baseline. LRG1 independently predicted albuminuria progression above traditional risk factors, including baseline eGFR and urine albumin to creatinine ratio. A 1-SD increment in LRG1 was associated with a 1.26-fold [95% confidence interval (CI), 1.04 to 1.53, P = 0.018] higher adjusted risk for albuminuria progression. The association of LRG1 with microalbuminuria to macroalbuminuria progression was stronger than its association with normoalbuminuria to microalbuminuria progression [odds ratio (OR), 1.51; 95% CI, 1.04 to 2.18, P = 0.029 vs OR, 1.09; 95% CI, 0.86 to 1.37, P = 0.486, per 1-SD LRG1 increment]. Also, LRG1 independently predicted CKD progression above traditional risk factors. A 1-SD increment in LRG1 was associated with a 1.48-fold (95% CI, 1.04 to 2.11, P = 0.032) higher adjusted risk for CKD progression. CONCLUSIONS Plasma LRG1 predicts both albuminuria and CKD progression beyond traditional risk factors. It may play a role in the pathologic pathway leading to progression of DKD in T2DM.
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Affiliation(s)
- Jian-Jun Liu
- Clinical Research Unit, Khoo Teck Puat Hospital, Singapore 768828, Singapore
| | - Sharon Li Ting Pek
- Clinical Research Unit, Khoo Teck Puat Hospital, Singapore 768828, Singapore
| | - Kevin Ang
- Clinical Research Unit, Khoo Teck Puat Hospital, Singapore 768828, Singapore
| | | | - Su Chi Lim
- Diabetes Centre, Khoo Teck Puat Hospital, Singapore 768828, Singapore
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Zhang X, Low S, Kumari N, Wang J, Ang K, Yeo D, Yip CC, Tavintharan S, Sum CF, Lim SC. Direct medical cost associated with diabetic retinopathy severity in type 2 diabetes in Singapore. PLoS One 2017; 12:e0180949. [PMID: 28700742 PMCID: PMC5507311 DOI: 10.1371/journal.pone.0180949] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2017] [Accepted: 06/13/2017] [Indexed: 11/19/2022] Open
Abstract
Diabetic retinopathy (DR) is a leading cause of vision-loss globally among type 2 diabetes (T2DM) patients. Information on the economic burden of DR in Singapore is limited. We aim to identify the total annual direct medical costs of DR at different stages, and to examine factors influencing the costs. Four hundreds and seventy T2DM patients who attended the Diabetes Centre in a secondary hospital in Singapore in 2011-2014 were included. Digital color fundus photographs were assessed for DR in a masked fashion. Retinopathy severity was further categorized into non-proliferative DR (NPDR), including mild, moderate and severe NPDR, and proliferative DR (PDR). Medical costs were assessed using hospital administrative data. DR was diagnosed in 172 (39.5%) patients, including 51 mild, 62 moderate and 18 severe NPDR, and 41 PDR. The median cost in DR [2012.0 (1111.2-4192.3)] was significantly higher than that in non-DR patients [1158.1 (724.1-1838.9)] (p<0.001). The corresponding costs for mild, moderate, severe NPDR and PDR were [1167.1 (895.4-2012.0)], [2212.0 (1215.5-3825.5)], [2717.5 (1444.0-6310.7)], and [3594.8.1 (1978.4-8427.7)], respectively. After adjustment, the corresponding cost ratios for mild, moderate, severe NPDR, and PDR relative to non-DR were 1.1 (p = 0.827), 1.8 (p = 0.003), 2.0 (p = 0.031) and 2.3 (p<0.001), respectively. The other factors affecting the total cost include smoking (ratio = 1.7, p = 0.019), neuropathy (ratio = 1.9, p = 0.001) and chronic kidney disease (CKD) (ratio = 1.4, p = 0.019). The presence and severity of DR was associated with increased direct medical costs in T2DM. Our results suggest that preventing progression of DR may reduce the economic burden of DR.
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Affiliation(s)
- Xiao Zhang
- Clinical Research Unit, Khoo Teck Puat Hospital, Singapore, Republic of Singapore
| | - Serena Low
- Clinical Research Unit, Khoo Teck Puat Hospital, Singapore, Republic of Singapore
| | - Neelam Kumari
- Department of ophthalmology and Visual Sciences, Khoo Teck Puat Hospital, Singapore, Republic of Singapore
| | - Jiexun Wang
- Clinical Research Unit, Khoo Teck Puat Hospital, Singapore, Republic of Singapore
| | - Keven Ang
- Clinical Research Unit, Khoo Teck Puat Hospital, Singapore, Republic of Singapore
| | - Darren Yeo
- Clinical Research Unit, Khoo Teck Puat Hospital, Singapore, Republic of Singapore
| | - Chee Chew Yip
- Department of ophthalmology and Visual Sciences, Khoo Teck Puat Hospital, Singapore, Republic of Singapore
| | - Subramaniam Tavintharan
- Department of Medicine, Khoo Teck Puat Hospital, Singapore, Republic of Singapore
- Diabetes Centre, Khoo Teck Puat Hospital, Singapore, Republic of Singapore
| | - Chee Fang Sum
- Department of Medicine, Khoo Teck Puat Hospital, Singapore, Republic of Singapore
- Diabetes Centre, Khoo Teck Puat Hospital, Singapore, Republic of Singapore
| | - Su Chi Lim
- Department of Medicine, Khoo Teck Puat Hospital, Singapore, Republic of Singapore
- Diabetes Centre, Khoo Teck Puat Hospital, Singapore, Republic of Singapore
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Zhang X, Low S, Sum CF, Tavintharan S, Yeoh LY, Liu J, Li N, Ang K, Lee SB, Tang WE, Lim SC. Arterial stiffness is an independent predictor for albuminuria progression among Asians with type 2 diabetes-A prospective cohort study. J Diabetes Complications 2017; 31:933-938. [PMID: 28392041 DOI: 10.1016/j.jdiacomp.2017.02.004] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2016] [Revised: 11/14/2016] [Accepted: 02/01/2017] [Indexed: 02/08/2023]
Abstract
AIM Albuminuria progression has been associated with renal deterioration in type 2 diabetes (T2DM). Central arterial stiffness can aggravate systemic vasculopathy by propagating elevated systolic and pulse pressures forward, thereby accentuating global vascular injury. We aim to investigate whether central arterial stiffness is an independent predictor for albuminuria progression in a multi-ethnic T2DM Asian cohort in Singapore. METHODS In a prospective cohort, 1012 T2DM patients were assessed at baseline and after a median follow-up of 3.1years. 880 patients with baseline normo- (urinary albumin-to-creatinine ratio (ACR)<30mg/g, n=579) and microalbuminuria (ACR=30-299mg/g, n=301) were divided into progression and non-progression groups according to ACR changes. Progression was defined as transition from normo- to microalbuminuria, micro- to macroalbuminuria, or normo- to macroalbuminuria. Central arterial stiffness was estimated by carotid-femoral pulse wave velocity (PWV) using applanation tonometry method. Stepwise multiple regression analysis was used to determine the predictor(s) for albuminuria progression. RESULTS Albuminuria progression occurred in 178 patients (20.2%). Baseline PWV was higher in progression (10.1±2.9m/s) than non-progression group (9.2±2.4m/s, p<0.001). 1-SD increase in baseline PWV was associated with albuminuria progression (OR=1.457, 95% CI, 1.236-1.718, p<0.001). Stepwise regression analysis identified that baseline PWV (OR=1.241, 95% CI, 1.033-1.490, p=0.021), BMI (OR=1.046, 95% CI, 1.012-1.080, p=0.008), nature log-transformed estimated glomerular filtration rate (LneGFR) (OR=0.320, 95% CI, 0.192-0.530, p=0.010) and LnACR (OR=1.344, 95% CI, 1.187-1.522, p=0.008) are predictors for albuminuria progression. CONCLUSION Increased central arterial stiffness at baseline predicted future progression of albuminuria. Our results suggest the potential benefit of ameliorating central arterial stiffness to retard albuminuria progression in T2DM.
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Affiliation(s)
- Xiao Zhang
- Clinical Research Unit, Khoo Teck Puat Hospital, Singapore 768828, Republic of Singapore
| | - Serena Low
- Clinical Research Unit, Khoo Teck Puat Hospital, Singapore 768828, Republic of Singapore
| | - Chee Fang Sum
- Diabetes Centre, Khoo Teck Puat Hospital, Singapore 768828, Republic of Singapore; Department of Medicine, Khoo Teck Puat Hospital, Singapore 768828, Republic of Singapore
| | - Subramaniam Tavintharan
- Diabetes Centre, Khoo Teck Puat Hospital, Singapore 768828, Republic of Singapore; Department of Medicine, Khoo Teck Puat Hospital, Singapore 768828, Republic of Singapore
| | - Lee Ying Yeoh
- Department of Medicine, Khoo Teck Puat Hospital, Singapore 768828, Republic of Singapore
| | - Jianjun Liu
- Clinical Research Unit, Khoo Teck Puat Hospital, Singapore 768828, Republic of Singapore
| | - Na Li
- Clinical Research Unit, Khoo Teck Puat Hospital, Singapore 768828, Republic of Singapore
| | - Keven Ang
- Clinical Research Unit, Khoo Teck Puat Hospital, Singapore 768828, Republic of Singapore
| | - Simon Bm Lee
- National Healthcare Group Polyclinics, Singapore 138543, Singapore
| | - Wern Ee Tang
- National Healthcare Group Polyclinics, Singapore 138543, Singapore
| | - Su Chi Lim
- Diabetes Centre, Khoo Teck Puat Hospital, Singapore 768828, Republic of Singapore; Department of Medicine, Khoo Teck Puat Hospital, Singapore 768828, Republic of Singapore.
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Moh MC, Sum CF, Tavintharan S, Ang K, Lee SBM, Tang WE, Lim SC. Baseline predictors of aortic stiffness progression among multi-ethnic Asians with type 2 diabetes. Atherosclerosis 2017; 260:102-109. [PMID: 28376407 DOI: 10.1016/j.atherosclerosis.2017.01.031] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2016] [Revised: 01/25/2017] [Accepted: 01/25/2017] [Indexed: 01/07/2023]
Abstract
BACKGROUND AND AIMS This 3-year prospective study aimed to identify baseline parameters that predicted the progression of carotid-femoral pulse wave velocity (cf-PWV), which was used to evaluate aortic stiffness, among Singapore's multi-ethnic Asians with type 2 diabetes (T2DM). METHODS The cf-PWV was measured by the gold-standard tonometry method in 994 T2DM subjects at baseline and follow-up. The annual rate of cf-PWV change was calculated, and individuals above the 90th percentile with rate≥1.42 m/s per year were regarded as rapid progressors (n = 104). In a subgroup analysis of subjects with normal cf-PWV at 1st visit (n = 611), incident aortic stiffness was defined as follow-up cf-PWV≥10 m/s (n = 188). RESULTS The total cohort (mean age:57 ± 10 years; 53.4% Chinese, 20.4% Malay, 22.9% Indian, 3.2% 'Others') displayed a median annual cf-PWV progression rate of 0.2 m/s. Adjusted multivariate regression analyses showed that baseline age, cf-PWV and body mass index (BMI) constantly predicted follow-up cf-PWV, annual cf-PWV progression rate, rapid cf-PWV progression, and incident aortic stiffness. Paradoxically, lower baseline cf-PWV was associated with elevated annual cf-PWV progression rate and rapid progressors. This inverse relationship remained significant across ethnicities after ethnic stratification. Higher BMI independently predicted cf-PWV progression in Chinese and Indians, but not in Malay and 'Others' ethnic groups. Increased age was a significant predictor in Chinese and 'Others' ethnicities. CONCLUSIONS We demonstrated that baseline BMI is a modifiable independent risk factor of cf-PWV progression and incident aortic stiffness. Therefore, better obesity management may impede aortic stiffness in Singapore's T2DM patients, especially in the Chinese and Indians.
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Affiliation(s)
- Mei Chung Moh
- Clinical Research Unit, Khoo Teck Puat Hospital, 90 Yishun Central, Singapore 768828, Singapore
| | - Chee Fang Sum
- Diabetes Centre, Khoo Teck Puat Hospital, 90 Yishun Central, Singapore 768828, Singapore
| | | | - Keven Ang
- Clinical Research Unit, Khoo Teck Puat Hospital, 90 Yishun Central, Singapore 768828, Singapore
| | - Simon Biing Ming Lee
- National Healthcare Group Polyclinics, 3 Fusionopolis Link, Nexus@one-north, South Tower, # 05-10, Singapore 138543, Singapore
| | - Wern Ee Tang
- National Healthcare Group Polyclinics, 3 Fusionopolis Link, Nexus@one-north, South Tower, # 05-10, Singapore 138543, Singapore
| | - Su Chi Lim
- Diabetes Centre, Khoo Teck Puat Hospital, 90 Yishun Central, Singapore 768828, Singapore.
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Cardoso CRL, Salles GF. Aortic Stiffness as a Surrogate Endpoint to Micro- and Macrovascular Complications in Patients with Type 2 Diabetes. Int J Mol Sci 2016; 17:2044. [PMID: 27929441 PMCID: PMC5187844 DOI: 10.3390/ijms17122044] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2016] [Revised: 11/27/2016] [Accepted: 11/29/2016] [Indexed: 12/22/2022] Open
Abstract
Increased aortic stiffness has been recognized as a predictor of adverse cardiovascular outcomes in some clinical conditions, such as in patients with arterial hypertension and end-stage renal disease, in population-based samples and, more recently, in type 2 diabetic patients. Patients with type 2 diabetes have higher aortic stiffness than non-diabetic individuals, and increased aortic stiffness has been correlated to the presence of micro- and macrovascular chronic diabetic complications. We aimed to review the current knowledge on the relationships between aortic stiffness and diabetic complications, their possible underlying physiopathological mechanisms, and their potential applications to clinical type 2 diabetes management.
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Affiliation(s)
- Claudia R L Cardoso
- Department of Internal Medicine, School of Medicine and University Hospital Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rua Rodolpho Rocco 255, Cidade Universitária, Rio de Janeiro-RJ 21941-901, Brazil.
| | - Gil F Salles
- Department of Internal Medicine, School of Medicine and University Hospital Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rua Rodolpho Rocco 255, Cidade Universitária, Rio de Janeiro-RJ 21941-901, Brazil.
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Kim YS, Lee DH, Chae HS, Lee TK, Sohn TS, Jeong SC, Kim HY, Lee JI, Song JY, Yeo CD, Lee YB, Ahn HS, Hong M, Han K. Disability of Hearing Impairment Is Positively Associated With Urine Albumin/Creatinine Ratio in Korean Adults: The 2011-2012 Korea National Health and Nutrition Examination Survey. Clin Exp Otorhinolaryngol 2016; 9:212-9. [PMID: 27416740 PMCID: PMC4996098 DOI: 10.21053/ceo.2015.01368] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2015] [Revised: 10/05/2015] [Accepted: 10/06/2015] [Indexed: 01/19/2023] Open
Abstract
OBJECTIVES The aim of this study was to determine whether chronic kidney disease (CKD) is associated with hearing thresholds in the nationwide, large-scaled Korean population. METHODS This study analyzed the data of 9,798 subjects of 19 years and older (4,387 males and 5,411 females). Urine albumin-to-creatinine ratio (ACR) was measured from first-voided spot urine samples. The air-conduction hearing threshold was measured at 0.5, 1, 2, 3, 4, and 6 kHz and pure tone audiogram (PTA) average was calculated as the four-frequency average of 0.5, 1, 2, and 4 kHz. RESULTS Urine ACR was significantly correlated with the PTA average of better ear in both genders, especially at 3 and 6 kHz in males and at 1, 3, 4, and 6 kHz in females. After adjusting, urine ACR also increased the risk of hearing loss in female, especially if urine ACR was 30 mg/g and more (odds ratio, 1.636-2.229. This study showed that the degree of hearing loss was significantly different according to categories of urine ACR in both genders. Hearing loss without disability was found less but that with bilateral hearing disability was found more as urine ACR increased. In generally, prevalence of hearing loss with disability was higher in males than females. CONCLUSION This study demonstrated that urine ACR was significantly correlated with the PTA average of better ear in Korean adults of both genders. This study suggests that clinicians should carefully monitor the hearing level for subjects with elevated urine ACR, even though high urine ACR within the normal range.
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Affiliation(s)
- Young Soo Kim
- Epidemiology Study Cluster of Uijeongbu St. Mary’s Hospital, Uijeongbu St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Uijeongbu, Korea
| | - Dong-Hee Lee
- Epidemiology Study Cluster of Uijeongbu St. Mary’s Hospital, Uijeongbu St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Uijeongbu, Korea
| | - Hiun Suk Chae
- Epidemiology Study Cluster of Uijeongbu St. Mary’s Hospital, Uijeongbu St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Uijeongbu, Korea
| | - Tae-Kyu Lee
- Epidemiology Study Cluster of Uijeongbu St. Mary’s Hospital, Uijeongbu St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Uijeongbu, Korea
| | - Tae Seo Sohn
- Epidemiology Study Cluster of Uijeongbu St. Mary’s Hospital, Uijeongbu St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Uijeongbu, Korea
| | - Seong Cheol Jeong
- Epidemiology Study Cluster of Uijeongbu St. Mary’s Hospital, Uijeongbu St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Uijeongbu, Korea
| | - Hee Yeon Kim
- Epidemiology Study Cluster of Uijeongbu St. Mary’s Hospital, Uijeongbu St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Uijeongbu, Korea
| | - Jae-Im Lee
- Epidemiology Study Cluster of Uijeongbu St. Mary’s Hospital, Uijeongbu St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Uijeongbu, Korea
| | - Jae Yen Song
- Epidemiology Study Cluster of Uijeongbu St. Mary’s Hospital, Uijeongbu St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Uijeongbu, Korea
| | - Chang Dong Yeo
- Epidemiology Study Cluster of Uijeongbu St. Mary’s Hospital, Uijeongbu St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Uijeongbu, Korea
| | - Young Bok Lee
- Epidemiology Study Cluster of Uijeongbu St. Mary’s Hospital, Uijeongbu St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Uijeongbu, Korea
| | - Hyo-Suk Ahn
- Epidemiology Study Cluster of Uijeongbu St. Mary’s Hospital, Uijeongbu St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Uijeongbu, Korea
| | - Mihee Hong
- Epidemiology Study Cluster of Uijeongbu St. Mary’s Hospital, Uijeongbu St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Uijeongbu, Korea
| | - Kyungdo Han
- Department of Biostatistics, College of Medicine, The Catholic University of Korea, Seoul, Korea
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Ethnic disparity in central arterial stiffness and its determinants among Asians with type 2 diabetes. Atherosclerosis 2015; 242:22-8. [DOI: 10.1016/j.atherosclerosis.2015.06.019] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2015] [Revised: 05/29/2015] [Accepted: 06/16/2015] [Indexed: 02/05/2023]
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Yoon HE, Kim ES, Mo EY, Shin SJ, Moon SD, Han JH. High normal albuminuria is associated with arterial stiffness and carotid atherosclerosis in Korean patients with type 2 diabetes. Nutr Metab Cardiovasc Dis 2015; 25:787-794. [PMID: 25921847 DOI: 10.1016/j.numecd.2015.03.011] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2015] [Revised: 03/16/2015] [Accepted: 03/21/2015] [Indexed: 10/23/2022]
Abstract
BACKGROUND AND AIMS Current evidence suggests that high normal albuminuria is significantly associated with increased cardiovascular risk. This study investigated the association between urine albumin-to-creatinine ratio (ACR) within the normal range and subclinical atherosclerosis in Korean patients with type 2 diabetes. METHODS AND RESULTS This cross-sectional study involved 521 type 2 diabetic patients with normoalbuminuria. Brachial-ankle pulse wave velocity (baPWV) measurement and ultrasound assessment of carotid atherosclerosis was done. Subclinical atherosclerosis was assessed by the presence of high baPWV (>1682 cm/s), carotid atherosclerosis (intima-media thickness >0.8 mm or the presence of plaques), and carotid stenosis (≥50% of luminal narrowing). Across the tertiles of ACR, there was a trend for an increasing prevalence of high baPWV (16.8%, 20.0%, and 38.2%, P < 0.001), carotid atherosclerosis (46.9%, 55.4%, and 64.7%, P < 0.001), and carotid stenosis (12.7%, 16.0%, and 30.1%, P < 0.001). In multivariate analysis, patients in the highest ACR tertile had an odds ratio of 2.05 (95% confidence interval [CI], 1.13-3.72, P = 0.019) for high baPWV, 1.78 (95% CI, 1.08-2.93, P = 0.024) for carotid atherosclerosis, and 2.72 (95% CI, 1.44-5.11, P = 0.002) for carotid stenosis compared to those in the lowest tertile. The relation of ACR with carotid atherosclerosis and stenosis remained significant even in patients without diabetic retinopathy. CONCLUSION High normal albuminuria was significantly associated with atherosclerotic vascular changes, independent of retinopathy and other cardiovascular risk factors. High normal albuminuria may be an early marker for subclinical atherosclerosis in type 2 diabetes.
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Affiliation(s)
- H E Yoon
- Department of Internal Medicine, The Catholic University of Korea, College of Medicine, Republic of Korea; Division of Nephrology, Department of Internal Medicine, Incheon St. Mary's Hospital, Incheon, Republic of Korea
| | - E S Kim
- Department of Internal Medicine, The Catholic University of Korea, College of Medicine, Republic of Korea; Division of Endocrinology and Metabolism, Department of Internal Medicine, Incheon St. Mary's Hospital, Incheon, Republic of Korea.
| | - E Y Mo
- Department of Internal Medicine, The Catholic University of Korea, College of Medicine, Republic of Korea; Division of Endocrinology and Metabolism, Department of Internal Medicine, Incheon St. Mary's Hospital, Incheon, Republic of Korea
| | - S J Shin
- Department of Internal Medicine, The Catholic University of Korea, College of Medicine, Republic of Korea; Division of Nephrology, Department of Internal Medicine, Incheon St. Mary's Hospital, Incheon, Republic of Korea
| | - S D Moon
- Department of Internal Medicine, The Catholic University of Korea, College of Medicine, Republic of Korea; Division of Endocrinology and Metabolism, Department of Internal Medicine, Incheon St. Mary's Hospital, Incheon, Republic of Korea
| | - J H Han
- Department of Internal Medicine, The Catholic University of Korea, College of Medicine, Republic of Korea; Division of Endocrinology and Metabolism, Department of Internal Medicine, Incheon St. Mary's Hospital, Incheon, Republic of Korea
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Kalaitzidis RG, Karasavvidou DP, Tatsioni A, Pappas K, Katatsis G, Liontos A, Elisaf MS. Albuminuria as a marker of arterial stiffness in chronic kidney disease patients. World J Nephrol 2015; 4:406-414. [PMID: 26167465 PMCID: PMC4491932 DOI: 10.5527/wjn.v4.i3.406] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2014] [Revised: 12/22/2014] [Accepted: 04/09/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To access the association between albuminuria levels and arterial stiffness in non-diabetic patients with hypertension and chronic kidney disease (CKD) stages 1-2, treated with renin angiotensin blockade agents plus other hypertensive drugs when needed.
METHODS: One hundred fifteen patients [median age 52 years (68% males)] were consequently enrolled in the study. For each patient, we recorded gender, age, body mass index (BMI), peripheral systolic blood pressure (pSBP), peripheral diastolic blood pressure, peripheral pulse pressure, central systolic blood pressure (cSBP), central diastolic blood pressure (cDBP), central pulse pressure (cPP), hematocrit, hemoglobin, hsCRP, total cholesterol triglycerides, high-density lipoprotein-C, low-density lipoprotein-C, calcium, phosphorus, parathormone, and albumin, as well as 24 h urine albumin excretion. According to 24-h urine albumin collection, patients were then classified as those with moderately increased albuminuria (formerly called macroalbuminuria) (≤ 300 mg/d) and those with severely increased albuminuria (formerly called macroaluminuria (> 300 mg/d). We considered aortic stiffness (AS) indices [carotid femoral pulse wave velocity (PWVc-f) and augmentation index (AIx)] as primary outcomes of the study. We explored potential correlations between severely increased albuminuria and AS indices using a multiple linear regression model.
RESULTS: Fifty-eight patients were included in the moderately increased albuminuria group and 57 in the severely increased albuminuria. Blood pressure measurements of the study population were 138 ± 14/82 ± 1.3 mmHg (systolic/diastolic). There were no significant differences in age, sex, and BP measurements between the two groups. Patients with severely increased albuminuria had higher PWV and AIx than patients with moderately increased albuminuria (P < 0.02, P < 0.004, respectively). In addition these patients exhibited higher BMI (P < 0.03), hsCRP (P < 0.001), and fibrinogen levels (P < 0.02) compared to patients with moderately increased albuminuria. In multivariate linear regression analysis, severely increased albuminuria (β = 1.038, P < 0.010) pSBP (β = 0.028, P < 0.034) and Ht (β = 0.171, P = 0.001) remained independent determinants of the increased PWVc-f. Similarly, severely increased albuminuria (β = 4.385, P < 0.012), cSBP (β = 0.242, P < 0.001), cPP (β = 0.147, P < 0.01) and Ht levels (β = 0.591, P < 0.013) remained independent determinants of increased AIx.
CONCLUSION: These findings demonstrate an independent association between AS indices and severely increased albuminuria in non-diabetic, hypertensive patients with CKD stages 1-2 treated with renin angiotensin aldosterone system blockers.
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Chai Kheng EY, Chee Fang S, Chang S, Kiat Mun SL, Su Chi L, Lee Ying Y, Xiao Wei N, Wern Ee T, Biing Ming SL, Tavintharan S. Low-density lipoprotein cholesterol levels in adults with type 2 diabetes: an alternative equation for accurate estimation and improved cardiovascular risk classification. Diab Vasc Dis Res 2014; 11:431-9. [PMID: 25205607 DOI: 10.1177/1479164114547703] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Low-density lipoprotein cholesterol (LDL-C) is a major risk factor for atherosclerotic disease. Despite its limitations, Friedewald-calculated LDL-C (F-LDL-C) remains widely used for LDL-C determination. In this observational study of 1999 adults with type 2 diabetes mellitus (T2DM), we compare the accuracy of F-LDL-C to directly measured LDL-C (M-LDL-C) and derived and validated a new [SMART2D (Singapore Study of MAcro-angiopathy and Micro-Vascular Reactivity in Type 2 Diabetes)] formula to estimate LDL-C. From 1000 randomly selected patients, M-LDL-C was compared to F-LDL-C. Using multiple linear regression to identify independent predictors for M-LDL-C, the SMART2D equation was derived and subsequently validated in the next 981 patients. F-LDL-C was 0.367 (0.216) mmol/L lower than M-LDL-C. This difference was -0.009 (0.189) for SMART2D-LDL-C. Using F-LDL-C, 27% with M-LDL-C ≥2.6 mmol/L were classified as LDL-C <2.6 mmol/L, reduced to 2.1% when using SMART2D-LDL-C. With F-LDL-C, misclassification was greater when triglycerides were ≥2.2 mmol/L, especially for the lower LDL-C cut-offs (1.8 and 2.6 mmol/L), and this was markedly improved with SMART2D-LDL-C. In conclusion, in T2DM, F-LDL-C underestimates M-LDL-C, with misclassifications that may potentially have an impact on therapeutic decisions in T2DM. The SMART2D equation improves accuracy of estimate, reducing misclassifications. Trials will be needed to ascertain the clinical significance of these findings.
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Affiliation(s)
- Ester Yeoh Chai Kheng
- Diabetes Centre, Khoo Teck Puat Hospital, Singapore Division of Endocrinology, Medicine Unit 2, Department of Medicine, Khoo Teck Puat Hospital, Singapore
| | - Sum Chee Fang
- Diabetes Centre, Khoo Teck Puat Hospital, Singapore Division of Endocrinology, Medicine Unit 2, Department of Medicine, Khoo Teck Puat Hospital, Singapore
| | - Su Chang
- Clinical Research Unit, Khoo Teck Puat Hospital, Singapore
| | | | - Lim Su Chi
- Diabetes Centre, Khoo Teck Puat Hospital, Singapore Division of Endocrinology, Medicine Unit 2, Department of Medicine, Khoo Teck Puat Hospital, Singapore Clinical Research Unit, Khoo Teck Puat Hospital, Singapore
| | - Yeoh Lee Ying
- Division of Nephrology, Medicine Unit 2, Department of Medicine, Khoo Teck Puat Hospital, Singapore
| | - Ng Xiao Wei
- Clinical Research Unit, Khoo Teck Puat Hospital, Singapore
| | - Tang Wern Ee
- Clinical Research Unit, National Healthcare Group Polyclinics, Singapore
| | | | - S Tavintharan
- Diabetes Centre, Khoo Teck Puat Hospital, Singapore Division of Endocrinology, Medicine Unit 2, Department of Medicine, Khoo Teck Puat Hospital, Singapore Clinical Research Unit, Khoo Teck Puat Hospital, Singapore
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Liu JJ, Sum CF, Tavintharan S, Yeoh LY, Ng XW, Moh AMC, Lee S, Tang WE, Lim SC. Obesity is a determinant of arterial stiffness independent of traditional risk factors in Asians with young-onset type 2 diabetes. Atherosclerosis 2014; 236:286-91. [DOI: 10.1016/j.atherosclerosis.2014.07.017] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2014] [Revised: 07/15/2014] [Accepted: 07/16/2014] [Indexed: 12/21/2022]
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Tavintharan S, Pek LTS, Liu JJ, Ng XW, Yeoh LY, Su Chi L, Chee Fang S. Osteoprotegerin is independently associated with metabolic syndrome and microvascular complications in type 2 diabetes mellitus. Diab Vasc Dis Res 2014; 11:359-62. [PMID: 25005034 DOI: 10.1177/1479164114539712] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
AIMS Osteoprotegerin (OPG) is a glycoprotein from tumour necrosis factor receptor superfamily, responsible for osteoclastogenesis inhibition and associated with arterial calcification and stiffness. We describe the association between metabolic syndrome (MS) and OPG in type 2 diabetes mellitus patients. METHODOLOGY We consecutively enrolled 1220 patients from our institution's Diabetes Centre from August 2011. Anthropometric data such as fasting blood/urine were obtained, and OPG was measured by enzyme-linked immunosorbent assay (ELISA). RESULTS Mean (standard deviation (SD)) of age and diabetes duration was 57.4 (10.9) years and 11.2 (8.9) years, respectively. Prevalence of MS was 64.3% (95% confidence interval (CI): 61.3%-67.2%) and associated with significantly higher OPG (5.44 vs 4.47 pmol/L) and microvascular complications. The presence of microvascular complications was associated with higher OPG: nephropathy (5.54 (2.20) vs 4.65 (1.70) pmol/L, p < 0.0001), neuropathy (6.33 (2.64) vs 5.06 (1.91) pmol/L, p < 0.0001) and retinopathy (6.08 (2.47) vs 5.00 (1.95) pmol/L, p < 0.0001). After adjusting for age, gender, ethnicity, glucose and microvascular complications, OPG remained an independent predictor of MS: (odds ratio (OR) = 1.102 (95% CI: 1.015-1.196), p = 0.021). CONCLUSION Higher OPG levels were associated with risk of MS and microvascular complications. Studies are needed to test whether OPG could be a useful biomarker identifying patients at risk of vascular complications and whether further exploration of this pathway may lead novel therapeutic options.
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Affiliation(s)
- S Tavintharan
- Diabetes Centre, Khoo Teck Puat Hospital, Singapore Division of Endocrinology, Khoo Teck Puat Hospital, Singapore
| | | | - Jian Jun Liu
- Clinical Research Unit, Khoo Teck Puat Hospital, Singapore
| | - Xiao Wei Ng
- Clinical Research Unit, Khoo Teck Puat Hospital, Singapore
| | - Lee Ying Yeoh
- Division of Nephrology, Department of Medicine, Khoo Teck Puat Hospital, Singapore
| | - Lim Su Chi
- Diabetes Centre, Khoo Teck Puat Hospital, Singapore Division of Endocrinology, Khoo Teck Puat Hospital, Singapore
| | - Sum Chee Fang
- Diabetes Centre, Khoo Teck Puat Hospital, Singapore Division of Endocrinology, Khoo Teck Puat Hospital, Singapore
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