|
1
|
Mirijello A, Pacilli G, Siena A, Mangiacotti A, D'Errico MM, Dilalla D, Lamacchia O, Fontana A, Copetti M, Piscitelli P, Targher G, De Cosmo SA. The Fibrosis-4 index predicts all-cause mortality in a cohort of patients at high cardiovascular risk partly through glomerular filtration rate reduction. Nutr Metab Cardiovasc Dis 2025; 35:103768. [PMID: 39561690 DOI: 10.1016/j.numecd.2024.10.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2024] [Revised: 09/21/2024] [Accepted: 10/07/2024] [Indexed: 11/21/2024]
Abstract
BACKGROUND AND AIM Fibrosis-4 (FIB-4) index is a widely used test for non-invasively assessing liver fibrosis. We aimed to investigate the association between FIB-4 index and risk of all-cause mortality in patients at high cardiovascular (CV) risk and to determine whether coexisting renal dysfunction mediates this association. METHODS AND RESULTS Single-center prospective study of 994 patients with established or suspected coronary artery disease undergoing coronary angiography, followed for a median of 44 months. Mortality data were obtained through the Italian Health Card Database. At baseline, the median FIB-4 index was greater in deceased vs. alive patients (1.71 vs. 1.38, p < 0.001) and in those with reduced eGFR than in those with normal eGFR (1.65 vs. 1.37, p < 0.001). For each unit increase in the baseline log-FIB-4 index, the risk of all-cause mortality sharply increased during the follow-up (hazard ratio [HR] 2.31, 95%CI 1.31-4.08, p = 0.004). Similarly, assuming the lowest baseline FIB-4 risk category as the reference, the risk of all-cause mortality progressively increased across the indeterminate (HR 1.82, 95%CI 1.18-2.82, p = 0.007) and the highest baseline FIB-4 risk categories (HR 2.33, 95%CI 1.37-3.97; p = 0.002). A causal mediation analysis showed that about one-third of the effect of FIB-4 index on mortality risk was mediated by reduced eGFR (32.8 %, p = 0.01). CONCLUSIONS Increased FIB-4 index predicts the long-term risk of all-cause mortality in patients at high CV risk, and this risk is, at least in part, mediated by reduced eGFR. Further prospective studies are needed to confirm these findings.
Collapse
Affiliation(s)
- Antonio Mirijello
- Unit of Internal Medicine, Fondazione IRCCS Casa Sollievo Della Sofferenza, 71013, San Giovanni Rotondo, Italy.
| | - Gabriella Pacilli
- Unit of Internal Medicine, Fondazione IRCCS Casa Sollievo Della Sofferenza, 71013, San Giovanni Rotondo, Italy
| | - Antonio Siena
- Unit of Internal Medicine, Fondazione IRCCS Casa Sollievo Della Sofferenza, 71013, San Giovanni Rotondo, Italy
| | - Antonio Mangiacotti
- Unit of Internal Medicine, Fondazione IRCCS Casa Sollievo Della Sofferenza, 71013, San Giovanni Rotondo, Italy
| | - Maria Maddalena D'Errico
- Unit of Geriatrics, Fondazione IRCCS Casa Sollievo Della Sofferenza, 71013 San Giovanni Rotondo, Italy
| | - Daria Dilalla
- Endocrinology Unit, Department of Medical Sciences, University of Foggia, Foggia, Italy
| | - Olga Lamacchia
- Endocrinology Unit, Department of Medical Sciences, University of Foggia, Foggia, Italy
| | - Andrea Fontana
- Unit of Biostatistics, Fondazione IRCCS Casa Sollievo Della Sofferenza, 71013, San Giovanni Rotondo, Italy
| | - Massimiliano Copetti
- Unit of Biostatistics, Fondazione IRCCS Casa Sollievo Della Sofferenza, 71013, San Giovanni Rotondo, Italy
| | - Pamela Piscitelli
- Unit of Internal Medicine, Fondazione IRCCS Casa Sollievo Della Sofferenza, 71013, San Giovanni Rotondo, Italy.
| | - Giovanni Targher
- Metabolic Diseases Research Unit, IRCCS Sacro Cuore - Don Calabria Hospital, 37024, Negrar di Valpolicella VR, Italy; Department of Medicine, University of Verona Faculty of Medicine and Surgery, 37126 Verona, Italy
| | - Salvatore A De Cosmo
- Unit of Internal Medicine, Fondazione IRCCS Casa Sollievo Della Sofferenza, 71013, San Giovanni Rotondo, Italy.
| |
Collapse
|
|
2
|
Pacilli G, Piscitelli P, D'Errico MM, Mangiacotti A, Siena A, Buglio AL, Vendemiale G, Fontana A, Copetti M, Mirijello A, De Cosmo SA. Association between R 2CHA 2DS 2-VASc score and three-vessel coronary artery disease in a large population at high cardiovascular risk. Intern Emerg Med 2024; 19:1877-1885. [PMID: 38970758 DOI: 10.1007/s11739-024-03679-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2024] [Accepted: 06/11/2024] [Indexed: 07/08/2024]
Abstract
Coronary artery disease (CAD), particularly three-vessel coronary disease (3VD), is the main cause of death in industrialized countries. Chronic kidney disease is an independent risk factor for CAD. The CHA2DS2-VASc score shows a good ability to predict CV events in high-risk population independently from atrial fibrillation. The aim of the present study was to evaluate the association between the R2CHA2DS2-VASc score and 3VD in a population of patients at high cardiovascular risk. Monocentric prospective study evaluated 1017 patients undergoing coronary angiography. The R2CHA2DS2-VASc score was obtained by adding 2 points to the CHA2DS2-VASc score in case of eGFR < 60 ml/min/1.73m2. Coronary lesions causing ≥ 50% reduction of a major epicardial vessel diameter were considered significant. Patients were grouped based on R2CHA2DS2-VASc tertiles and according to the severity of CAD: 3VD vs No-3VD. The 3VD group showed significantly higher R2CHA2DS2-VASc score than the No-3VD group (4.20 ± 2.18 vs 3.36 ± 2.06, p < 0.001). The risk of 3VD increased by 21% for every 1-point increase in the score (OR 1.21; 95% CI 1.13-1.28, p < 0.001). The prevalence of 3VD was higher among patients belonging to higher tertiles of R2CHA2DS2-VASc (17.2% vs 26.7% vs 33.6% for first, second, and third tertile respectively, p < 0.001) with a risk more than doubled for the third tertile compared to the first one (OR 2.45; 95% CI 1.71-3.49, p < 0.001). The R2CHA2DS2-VASc score is independently associated with 3VD in patients at high cardiovascular risk. The score could be considered a useful tool for clinicians to identify patients who are at high risk of 3VD.
Collapse
Affiliation(s)
- Gabriella Pacilli
- Units of Internal Medicine, Fondazione IRCCS Casa Sollievo Della Sofferenza, viale Cappuccini, 71013, San Giovanni Rotondo, Italy
| | - Pamela Piscitelli
- Units of Internal Medicine, Fondazione IRCCS Casa Sollievo Della Sofferenza, viale Cappuccini, 71013, San Giovanni Rotondo, Italy
| | - Maria Maddalena D'Errico
- Units of Internal Medicine, Fondazione IRCCS Casa Sollievo Della Sofferenza, viale Cappuccini, 71013, San Giovanni Rotondo, Italy
| | - Antonio Mangiacotti
- Units of Internal Medicine, Fondazione IRCCS Casa Sollievo Della Sofferenza, viale Cappuccini, 71013, San Giovanni Rotondo, Italy
| | - Antonio Siena
- Units of Internal Medicine, Fondazione IRCCS Casa Sollievo Della Sofferenza, viale Cappuccini, 71013, San Giovanni Rotondo, Italy
| | - Aurelio Lo Buglio
- Department of Medical and Surgical Sciences, University of Foggia, Viale Pinto 1, 71122, Foggia, Italy
| | - Gianluigi Vendemiale
- Department of Medical and Surgical Sciences, University of Foggia, Viale Pinto 1, 71122, Foggia, Italy
| | - Andrea Fontana
- Unit of Biostatistics, Fondazione IRCCS Casa Sollievo Della Sofferenza, Viale Cappuccini, 71013, San Giovanni Rotondo, Italy
| | - Massimiliano Copetti
- Unit of Biostatistics, Fondazione IRCCS Casa Sollievo Della Sofferenza, Viale Cappuccini, 71013, San Giovanni Rotondo, Italy
| | - Antonio Mirijello
- Units of Internal Medicine, Fondazione IRCCS Casa Sollievo Della Sofferenza, viale Cappuccini, 71013, San Giovanni Rotondo, Italy.
| | - Salvatore A De Cosmo
- Units of Internal Medicine, Fondazione IRCCS Casa Sollievo Della Sofferenza, viale Cappuccini, 71013, San Giovanni Rotondo, Italy.
| |
Collapse
|
|
3
|
Yoo JH, Kim JY, Kim JH. Association Between Continuous Glucose Monitoring-Derived Glycemia Risk Index and Albuminuria in Type 2 Diabetes. Diabetes Technol Ther 2023; 25:726-735. [PMID: 37335748 DOI: 10.1089/dia.2023.0165] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 06/21/2023]
Abstract
Background: The glycemia risk index (GRI) is a new composite metric derived from continuous glucose monitoring (CGM) data to assess the quality of glycemia. This study investigates the association between the GRI and albuminuria. Methods: Professional CGM and urinary albumin-to-creatinine ratio (UACR) data from 866 individuals with type 2 diabetes were retrospectively reviewed. Albuminuria and macroalbuminuria were defined as one or more UACR measurements ≥30 and ≥300 mg/g, respectively. Results: The overall prevalence of albuminuria and macroalbuminuria was 36.6% and 13.9%, respectively. Participants with a higher UACR had a significantly higher hyperglycemia component and GRI score than those with a lower UACR (all P < 0.001), although the hypoglycemia component did not differ among the groups. Multiple logistic regression analyses that adjusted for various factors affecting albuminuria revealed that the odds ratio (OR) of albuminuria was 1.13 (95% confidence interval [CI]: 1.02-1.27, P = 0.039) per increase in the GRI zone. The results were similar for the risk of macroalbuminuria (OR: 1.42 [95% CI: 1.20-1.69], P < 0.001), and that association remained after adjusting for glycated hemoglobin (OR: 1.31 [95% CI: 1.10-1.58], P = 0.004). Conclusions: GRI is strongly associated with albuminuria, especially macroalbuminuria, in type 2 diabetes.
Collapse
Affiliation(s)
- Jee Hee Yoo
- Division of Endocrinology and Metabolism, Department of Medicine, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea
| | - Ji Yoon Kim
- Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Jae Hyeon Kim
- Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| |
Collapse
|
|
4
|
Piscitelli P, D'Errico MM, Vigna C, Marchese N, Lamacchia O, Fontana A, Copetti M, Pontremoli R, Mirijello A, De Cosmo SA. Albuminuria improves R 2CHA 2DS 2-VASc score in predicting mortality in high cardiovascular risk population. Nutr Metab Cardiovasc Dis 2023; 33:1591-1598. [PMID: 37263913 DOI: 10.1016/j.numecd.2023.05.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2023] [Accepted: 05/10/2023] [Indexed: 06/03/2023]
Abstract
BACKGROUND AND AIMS The CHA2DS2-VASc score estimates the risk of cardioembolism in patients with atrial fibrillation (AF). It also predicts vascular events and death in different clinical settings, even in the absence of AF. The R2CHA2DS2-VASc score, obtained by adding the glomerular filtration rate to CHA2DS2-VASc, shows a higher prediction ability for new events and all-cause mortality. The present study aims to assess whether the addition of albuminuria to R2CHA2DS2-VASc score further improves its discrimination ability in predicting all-cause mortality in a sample of high cardiovascular risk population. METHODS AND RESULTS Prospective, monocentric, observational study, evaluating a subset of 737 subjects consecutively undergoing to coronary angiography at Coronary Unit of Scientific Institute "Casa Sollievo della Sofferenza" from June 2016 to December 2018. The presence of albuminuria was significantly associated with all-cause mortality (p < 0.0001). Any one-point increase of Alb-R2CHA2DS2-VASc score increased mortality of about 1.5-fold (adjusted HR 1.49; 95%CI: 1.37-1.63; p < 0.0001). Considering tertiles of Alb-R2CHA2DS2-VASc, the third tertile showed a 9.5-fold increased risk of mortality (HR 9.52; 95% CI: 5.15-17.60, p < 0.001). Comparing the two scores, the Alb-R2CHA2DS2-VASc score (C-statistic = 0.751; 95%CI: 0.69-0.81) outperformed the R2-CHA2DS2-VASc score (C-statistic = 0.736; 95%CI: 0.68-0.961) in predicting mortality (delta C-statistic = 0.015; 95%CI: 0.001-0.029). The better prediction ability of the Alb-R2CHA2DS2-VASc score was also proven by an IDI of 0.024 (p < 0.0001) and a relative IDI of 24.11% (p < 0.0001), with an NRI = 0.608 (p < 0.00001). CONCLUSIONS The addition of albuminuria to R2CHA2DS2-VASc significantly and independently predicts the risk of all-cause mortality in a sample of high CV risk patients. Moreover, Alb-R2CHA2DS2-VASc outperforms R2CHA2DS2-VASc.
Collapse
Affiliation(s)
- Pamela Piscitelli
- Unit of Internal Medicine, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, FG, Italy.
| | - Maria Maddalena D'Errico
- Unit of Internal Medicine, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, FG, Italy
| | - Carlo Vigna
- Unit of Cardiology, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, FG, Italy
| | - Nicola Marchese
- Unit of Cardiology, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, FG, Italy
| | - Olga Lamacchia
- Unit of Endocrinology, University of Foggia, Foggia, FG, Italy
| | - Andrea Fontana
- Biostatistics Unit, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy
| | - Massimiliano Copetti
- Biostatistics Unit, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy
| | - Roberto Pontremoli
- Dipartimento di Medicina Interna e Specialità Mediche, Università degli Studi di Genova, Italy; IRCCS Ospedale Policlinico San Martino, Genova, Italy
| | - Antonio Mirijello
- Unit of Internal Medicine, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, FG, Italy
| | - Salvatore A De Cosmo
- Unit of Internal Medicine, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, FG, Italy.
| |
Collapse
|
|
5
|
Lin CA, Li WC, Lin SY, Chen YC, Yu W, Huang HY, Xiong XJ, Chen JY. Gender differences in the association between insulin resistance and chronic kidney disease in a Chinese population with metabolic syndrome. Diabetol Metab Syndr 2022; 14:184. [PMID: 36461016 PMCID: PMC9716739 DOI: 10.1186/s13098-022-00956-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2021] [Accepted: 11/14/2022] [Indexed: 12/05/2022] Open
Abstract
BACKGROUND Insulin resistance (IR) was reported to be associated with renal function impairment, but little is known about the gender difference. Hence, our study aimed to investigate the relationship between IR (estimated by the homeostasis model assessment of IR (HOMA-IR) index) and chronic kidney disease (CKD) in a Chinese population with metabolic syndrome (MetS) and discern whether there was any gender disparity or not. METHODS This retrospective cross-sectional study enrolled 13,638 men and 10,450 women who received health examinations from 2013 to 2016 at Xiamen Chang Gung Hospital. Among the participants, 3,253 men (64.3%) and 1,808 women (35.7%) who had MetS and met the inclusion criteria were included for analysis. Spearman's correlation was conducted to analyze the relationship between HOMA-IR and cardio-metabolic risk factors. Multivariable linear regression was analyzed to explore the relationship between HOMA-IR and cardio-metabolic variables. Logistic regression analysis was performed to assess the association between HOMA-IR and CKD. RESULTS The median HOMA-IR and prevalence of CKD was 2.2 and 11.31%, respectively, for men and 2.09 and 15.93%, respectively, for women. In multivariable linear regression analysis, HOMA-IR was significant associated with estimated GFR, albumin/creatinine ratio in men. Multivariable logistic regression revealed a significant difference between HOMA-IR value and the prevalence of CKD in men but not in women (odds ratio in male = 1.21; 95% CI 1.14-1.28, p ≤ 0.001; odds ratio in female = 1.01; 95% CI 0.99-1.02, p = 0.38). CONCLUSIONS HOMA-IR was independently associated with CKD among men with MetS but not in women.
Collapse
Affiliation(s)
- Chieh-An Lin
- Department of Family Medicine, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan
| | - Wen-Cheng Li
- Department of Family Medicine, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Department of Health Management, Xiamen Chang Gung Hospital, Xiamen, China
| | - Szu-Yu Lin
- Department of Family Medicine, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan
| | - Yi-Chuan Chen
- Department of Family Medicine, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Wei Yu
- Department of Health Management, Xiamen Chang Gung Hospital, Xiamen, China
| | - Hsiung-Ying Huang
- Department of Pulmonary and Critical Care Medicine, Xiamen Chang Gung Hospital, Xiamen, China
| | - Xue-Jie Xiong
- Department of Oncology, Xiamen Chang Gung Hospital, Xiamen, China
| | - Jau-Yuan Chen
- Department of Family Medicine, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan.
- College of Medicine, Chang Gung University, Taoyuan, Taiwan.
| |
Collapse
|
|
6
|
D'Errico MM, Piscitelli P, Mirijello A, Santoliquido M, Salvatori M, Vigna C, Vendemiale G, Lamacchia O, Fontana A, Copetti M, Pontremoli R, De Cosmo SA. CHA2DS2-VASc and R2CHA2DS2-VASc scores predict mortality in high cardiovascular risk population. Eur J Clin Invest 2022; 52:e13830. [PMID: 35778894 DOI: 10.1111/eci.13830] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2022] [Revised: 06/30/2022] [Accepted: 06/30/2022] [Indexed: 11/28/2022]
Abstract
BACKGROUND The CHA2 DS2 -VASc score, widely used to estimate cardioembolic risk in patients with atrial fibrillation (AF), appears to be useful also in predicting vascular adverse events and death in different sets of patients without AF. The R2 CHA2 DS2 -VASc score, which includes renal impairment, allows a better prediction of death and thromboembolism in patients without AF. The aims of our study were to assess, in a large sample of patients at high cardiovascular (CV) risk, (i) the correlation between CHA2 DS2 -VASc and R2 CHA2 DS2 -VASc with all-cause mortality, and (ii) to compare the performances of CHA2 DS2 -VASc and R2 CHA2 DS2 -VASc in predicting all-cause mortality. METHODS In this single-centre prospective observational study, conducted at the Research Hospital 'Casa Sollievo della Sofferenza' between June 2016 and December 2018, 1017 CV patients at high risk of undergoing coronary angiography were enrolled. RESULTS CHA₂DS₂-VASc and R2 CHA2 DS2 -VASc scores significantly associated with all-cause mortality. For each one-point increase in CHA2 DS2 -VASc or R2 CHA2 DS2 -VASc scores, mortality increased by almost 1.5-fold. The R2 CHA2 DS2 -VASc score (C-statistic = 0.71; 95% CI = 0.65-76) outperformed the CHA2 DS2 -VASc score (C-statistic = 0.66; 95% CI = 0.61-0.71) in predicting 4-year mortality (delta C-statistic = 0.05; 95% CI = 0.02-0.07). The better predictive ability of the R-CHA2 DS2 -VASc score was also demonstrated by an IDI = 0.027 (95% CI = 0.021-0.034, p < .00001) and a relative IDI = 62.8% (95% CI = 47.9%-81.3%, p < .00001). The R2 CHA2 DS2 -VASc score correctly reclassified the patients with a NRI = 0.715 (95% = 0.544-0.940, p < .00001). CONCLUSIONS The CHA₂DS₂-VASc and R2 CHA2 DS2 -VASc scores are useful predictors of all-cause mortality in subjects at high CV risk, with the R2 CHA2 DS2 -VASc score being the best performer.
Collapse
Affiliation(s)
- Maria Maddalena D'Errico
- Unit of Internal Medicine, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy
| | - Pamela Piscitelli
- Unit of Internal Medicine, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy
| | - Antonio Mirijello
- Unit of Internal Medicine, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy
| | - Mariateresa Santoliquido
- Unit of Internal Medicine, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.,Geriatrics Residency School, University of Foggia, Foggia, Italy
| | - Mauro Salvatori
- Unit of Cardiology, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy
| | - Carlo Vigna
- Unit of Cardiology, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy
| | | | - Olga Lamacchia
- Unit of Endocrinology, University of Foggia, Foggia, Italy
| | - Andrea Fontana
- Biostatistics Unit, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy
| | - Massimiliano Copetti
- Biostatistics Unit, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy
| | - Roberto Pontremoli
- University of Genoa and IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Salvatore A De Cosmo
- Unit of Internal Medicine, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy
| |
Collapse
|
|
7
|
D'Errico MM, Piscitelli P, Mirijello A, Santoliquido M, Massa V, Salvatori M, Vigna C, Vendemiale G, Aucella F, Pontremoli R, De Cosmo SA. Low eGFR and albuminuria independently predict all-cause mortality in high-risk subjects undergoing coronary arteriography. Intern Emerg Med 2022; 17:695-701. [PMID: 34609678 DOI: 10.1007/s11739-021-02851-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2021] [Accepted: 09/12/2021] [Indexed: 12/19/2022]
Abstract
Individuals with Chronic Kidney Disease (CKD) are at high risk for cardiovascular morbidity and mortality. The aim of this study was to examine the relationship between renal dysfunction and all-cause mortality in a sample of subjects undergoing coronary angiography (CA). We evaluated 1017 subjects who consecutively underwent CA. Glomerular filtration rate (eGFR) was estimated by CKD-EPI and urinary albumin excretion reported as urinary albumin-to-creatinine ratio. Vital status was ascertained by interrogating the Italian Health Card Database. One-thousand-seventeen subjects (759 M/258F) were enrolled into the study from 2016 to 2018. One-hundred-fourteen deaths occurred during a median follow-up of 44 months. The whole population was divided in two subgroups according to the presence/absence of low eGFR (i.e. < 60 ml/min/1.73 m2). Subjects with low baseline eGFR had a worse clinical profile than subjects with preserved kidney function. The risk of death in subjects with eGFR < 60 ml/min/1.73 m2 was almost three times higher than in subjects with preserved kidney function: fully adjusted HR 2.70 (95% CI 1.56-4.67). The presence of albuminuria also predicted a high risk of death: fully adjusted HR 2.09 (95% CI 1.17-3.73) and HR 4.26 (95% CI 2.18-8.33), microalbuminuria or macroalbuminuria, respectively, being normoalbuminuria the reference group. Again, the increased risk remained significant after adjusting for several potential confounders. In conclusion, kidney disease measures (i.e. low eGFR or albuminuria) independently predict increased risk for all-cause death in a large sample of subjects undergoing CA. These results have a relevant clinical impact.
Collapse
Affiliation(s)
- Maria Maddalena D'Errico
- Unit of Internal Medicine, Fondazione IRCCS Casa Sollievo Della Sofferenza, Viale dei Cappuccini snc, 71013, San Giovanni Rotondo, FG, Italy
| | - Pamela Piscitelli
- Unit of Internal Medicine, Fondazione IRCCS Casa Sollievo Della Sofferenza, Viale dei Cappuccini snc, 71013, San Giovanni Rotondo, FG, Italy
| | - Antonio Mirijello
- Unit of Internal Medicine, Fondazione IRCCS Casa Sollievo Della Sofferenza, Viale dei Cappuccini snc, 71013, San Giovanni Rotondo, FG, Italy
| | - Mariateresa Santoliquido
- Unit of Internal Medicine, Fondazione IRCCS Casa Sollievo Della Sofferenza, Viale dei Cappuccini snc, 71013, San Giovanni Rotondo, FG, Italy
- Geriatrics Residency School, University of Foggia, Foggia, FG, Italy
| | - Valentina Massa
- Unit of Internal Medicine, Fondazione IRCCS Casa Sollievo Della Sofferenza, Viale dei Cappuccini snc, 71013, San Giovanni Rotondo, FG, Italy
| | - Mauro Salvatori
- Unit of Cardiology, Fondazione IRCCS Casa Sollievo Della Sofferenza, Viale Cappuccini snc, 71013, San Giovanni Rotondo, FG, Italy
| | - Carlo Vigna
- Unit of Cardiology, Fondazione IRCCS Casa Sollievo Della Sofferenza, Viale Cappuccini snc, 71013, San Giovanni Rotondo, FG, Italy
| | | | - Filippo Aucella
- Unit of Nephrology and Hemodialysis, Fondazione IRCCS Casa Sollievo Della Sofferenza, Viale Cappuccini snc, 71013, San Giovanni Rotondo, FG, Italy
| | - Roberto Pontremoli
- Università Degli Studi and IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Salvatore A De Cosmo
- Unit of Internal Medicine, Fondazione IRCCS Casa Sollievo Della Sofferenza, Viale dei Cappuccini snc, 71013, San Giovanni Rotondo, FG, Italy.
| |
Collapse
|
|
8
|
Piscitelli P, D'Errico MM, Mirijello A, Santoliquido M, Salvatori M, Vigna C, Marchese N, Vendemiale G, Copetti M, Pontremoli R, De Cosmo SA. Low GFR amplifies the association between coronary three-vessel disease and all-cause mortality. Nutr Metab Cardiovasc Dis 2022; 32:402-409. [PMID: 34893408 DOI: 10.1016/j.numecd.2021.09.036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2021] [Revised: 09/07/2021] [Accepted: 09/29/2021] [Indexed: 11/15/2022]
Abstract
BACKGROUND AND AIM Three vessels disease (3VD) has been associated with worse prognosis and higher mortality. Chronic kidney disease (CKD) is an independent risk factor for premature death, mostly due to coronary artery disease (CAD). We aim to examine the prognostic impact of 3VD on all-cause mortality in a cohort of high cardiovascular risk subjects undergoing coronary angiography (CA) and to explore whether low eGFR (<60 ml/min/1.73 m2) modulates the risk of all-cause mortality associated to 3VD. METHODS AND RESULTS One-thousand-seventeen subjects (759 M, mean age 68.4 ± 11 years) consecutive subjects undergoing CA from 2016 to 2018 were evaluated. Subjects were classified according to the severity of CAD as follows: group "three vessels disease" (3VD), and "no three vessels disease" (No 3VD). Serum creatinine was measured to estimate glomerular filtration rate (eGFR). The whole population was divided into 4 groups (A, B, C, D), according to the presence/absence of low eGFR and/or 3VD. One-hundred-fourteen deaths occurred (median follow-up:44 months). The risk of death in subjects with 3VD was almost 2-time higher than subject without 3VD (adjusted HR = 1.61; 95% CI 1.094-2.373, p = 0.0157). Among 4 subgroups, subjects with low eGFR and 3VD (Group D) had the highest risk of death (adjusted HR = 3.881; 95% CI 2.256-6.676, p < 0.0001). CONCLUSIONS Low eGFR significantly amplifies the risk of all-cause mortality associated to 3VD. Our results strengthen the role of kidney disease as a risk multiplier for cardiovascular and all-cause mortality and highlight the need to prevent its onset and progression.
Collapse
Affiliation(s)
- Pamela Piscitelli
- Unit of Internal Medicine, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), Italy
| | - Maria M D'Errico
- Unit of Internal Medicine, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), Italy
| | - Antonio Mirijello
- Unit of Internal Medicine, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), Italy
| | - Mariateresa Santoliquido
- Unit of Internal Medicine, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), Italy; Geriatrics Residency School, University of Foggia, Foggia (FG), Italy
| | - Mauro Salvatori
- Unit of Cardiology, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), Italy
| | - Carlo Vigna
- Unit of Cardiology, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), Italy
| | - Nicola Marchese
- Unit of Cardiology, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), Italy
| | | | - Massimiliano Copetti
- Unit of Biostatistics, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy
| | - Roberto Pontremoli
- Università degli Studi and IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Salvatore A De Cosmo
- Unit of Internal Medicine, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), Italy.
| |
Collapse
|
|
9
|
Adeva-Andany MM, Fernández-Fernández C, Funcasta-Calderón R, Ameneiros-Rodríguez E, Adeva-Contreras L, Castro-Quintela E. Insulin Resistance is Associated with Clinical Manifestations of Diabetic Kidney Disease (Glomerular Hyperfiltration, Albuminuria, and Kidney Function Decline). Curr Diabetes Rev 2022; 18:e171121197998. [PMID: 34789129 DOI: 10.2174/1573399818666211117122604] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2021] [Revised: 09/13/2021] [Accepted: 09/15/2021] [Indexed: 11/22/2022]
Abstract
Clinical features of diabetic kidney disease include glomerular hyperfiltration, albuminuria, and kidney function decline towards End-Stage Kidney Disease (ESKD). There are presently neither specific markers of kidney involvement in patients with diabetes nor strong predictors of rapid progression to ESKD. Serum-creatinine-based equations used to estimate glomerular filtration rate are notoriously unreliable in patients with diabetes. Early kidney function decline, reduced glomerular filtration rate, and proteinuria contribute to identifying diabetic patients at higher risk for rapid kidney function decline. Unlike proteinuria, the elevation of urinary albumin excretion in the range of microalbuminuria is frequently transient in patients with diabetes and does not always predict progression towards ESKD. Although the rate of progression of kidney function decline is usually accelerated in the presence of proteinuria, histological lesions of diabetes and ESKD may occur with normal urinary albumin excretion. No substantial reduction in the rate of ESKD associated with diabetes has been observed during the last decades despite intensified glycemic control and reno-protective strategies, indicating that existing therapies do not target underlying pathogenic mechanisms of kidney function decline. Very long-term effects of sodium-glucose transporters- 2 inhibitors and glucagon-like peptide-1 analogs remain to be defined. In patients with diabetes, glucagon secretion is typically elevated and induces insulin resistance. Insulin resistance is consistently and strongly associated with clinical manifestations of diabetic kidney disease, suggesting that reduced insulin sensitivity participates in the pathogenesis of the disease and may represent a therapeutic objective. Amelioration of insulin sensitivity in patients with diabetes is associated with cardioprotective and kidney-protective effects.
Collapse
Affiliation(s)
- María M Adeva-Andany
- Nephrology Division, Hospital General Juan Cardona, c/ Pardo Bazán s/n, 15406 Ferrol, Spain
| | | | | | | | | | - Elvira Castro-Quintela
- Nephrology Division, Hospital General Juan Cardona, c/ Pardo Bazán s/n, 15406 Ferrol, Spain
| |
Collapse
|
|
10
|
Na H, Wang R, Zheng HL, Chen XP, Zheng LY. Correlation between Insulin Resistance and Microalbuminuria Creatinine Ratio in Postmenopausal Women. Int J Endocrinol 2022; 2022:9583611. [PMID: 36072812 PMCID: PMC9444479 DOI: 10.1155/2022/9583611] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2022] [Revised: 07/06/2022] [Accepted: 07/07/2022] [Indexed: 11/17/2022] Open
Abstract
OBJECTIVE To study the relationship between insulin resistance and urinary microalbumin creatinine ratio in postmenopausal women. METHODS The selected research group comprised 104 postmenopausal women with type 2 diabetes who were admitted to the Department of Endocrinology in the green card center at the First Affiliated Hospital of Hainan Medical University between 2017 and 2019 inclusive. Ninety-eight postmenopausal women with the normal blood glucose metabolism hospitalized in the same period were used as the control group. The age, body mass index, systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate, fasting blood glucose, fasting insulin (FINS), glycosylated hemoglobin (HbA1c), total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C), and urinary albumin-creatinine ratio (UACR) were analyzed. The insulin resistance index (HOMR-IR) was calculated, and the correlation between IR and UACR was analyzed. RESULTS Levels of HOMA-IR, SBP, HbA1c, HDL-C, LDL-C, TC, TG, FPG, FINS, and UACR in the study group were higher than those in the control group, and a significant difference was found between the groups (P < 0.05). The level of DBP in the study group was lower than that in the control group, and the difference was statistically significant (P < 0.05). Pearson correlation analysis showed that UACR was positively correlated with HOMA-IR and HbA1c (r = 0.254, r = 0.565, P < 0.01). Multiple linear stepwise regression analysis further showed that HOMA-IR and age were positively correlated with UACR (P < 0.05). CONCLUSION There is a correlation between IR and UACR in postmenopausal women. IR is an independent risk factor for UACR.
Collapse
Affiliation(s)
- Han Na
- Department of Endocrinology, The First Affiliated Hospital of Hainan Medical University, Haikou 571000, China
| | - Rong Wang
- Department of Wound Repair, The First Affiliated Hospital of Hainan Medical University, Haikou 571000, China
| | - Hai-Long Zheng
- Department of Endocrinology, The First Affiliated Hospital of Hainan Medical University, Haikou 571000, China
| | - Xiao-Pan Chen
- Department of Wound Repair, The First Affiliated Hospital of Hainan Medical University, Haikou 571000, China
| | - Lin-Yang Zheng
- Department of Endocrinology, The First Affiliated Hospital of Hainan Medical University, Haikou 571000, China
| |
Collapse
|
|
11
|
Lin CA, Liu YP, Chen YC, Yu W, Xiong XJ, Huang HY, Li WC, Chen JY. Gender-specific and age-specific associations of the homoeostasis model assessment for IR (HOMA-IR) with albuminuria and renal function impairment: a retrospective cross-sectional study in Southeast China. BMJ Open 2021; 11:e053649. [PMID: 34921082 PMCID: PMC8685940 DOI: 10.1136/bmjopen-2021-053649] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/08/2022] Open
Abstract
OBJECTIVES The study aimed to investigate the association of insulin resistance (IR), which was estimated by the homoeostasis model assessment for IR (HOMA-IR), with albuminuria and renal function impairment in a general Chinese population. DESIGN A retrospective cross-sectional study. SETTING AND PARTICIPANTS A total of 13 742 adults (age: ≥18 years) who underwent a health check-up at a hospital in Southeast China during 2013-2014 were enrolled. 216 subjects were excluded due to lack of enough fasting time, be pregnant, have chronic diseases influencing metabolic functions or have glomerulonephritis, renal cancer, kidney transplant. Eventually, 7552 men and 5974 women were included for the present analysis. PRIMARY OUTCOME MEASURES The association of HOMA-IR with albuminuria and renal function impairment were analysed. The HOMA-IR cut-off value for detecting albuminuria and renal function impairment were determined. RESULTS An increase in the HOMA-IR quartile was significantly associated with the prevalence of albuminuria and renal function impairment in all men and women aged >45 years. The multivariable logistic regression analyses revealed a significant association of the HOMA-IR with albuminuria and renal function impairment in subjects aged >45 years of the fourth quartiles compared with those of the first quartile after adjusting for potential confounders (albuminuria: men OR, 2.39; 95% CI 1.51 to 3.79, p<0.001; women OR, 2.40; 95% CI 1.44 to 4.01; p=0.001; renal function impairment: men OR, 2.30; 95% CI 1.50 to 3.51; p<0.001; women OR, 2.20; 95% CI 1.35 to 3.58; p=0.002). The optimal cut-off value of HOMA-IR for detecting albuminuria and renal function impairment was 2.69 in men aged ≤45 years, 1.60 in men aged >45 years and 1.86 in women aged >45 years. CONCLUSIONS Our study revealed that HOMA-IR was significantly associated with albuminuria and renal function impairment in individuals aged >45 years.
Collapse
Affiliation(s)
- Chieh-An Lin
- Department of Family Medicine, Chang Gung Memorial Hospital Linkou Main Branch, Taoyuan, Taiwan
| | - Yu-Ping Liu
- Department of Endocrinology and Metabolism, Xiamen Chang Gung Hospital, Xiamen, Fujian, China
| | - Yi-Chuan Chen
- Department of Family Medicine, Chang Gung Memorial Hospital Linkou Main Branch, Taoyuan, Taiwan
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Wei Yu
- Department of Health Management, Xiamen Chang Gung Hospital, Xiamen, Fujian, China
| | - Xue-Jie Xiong
- Department of Oncology, Xiamen Chang Gung Hospital, Xiamen, Fujian, China
| | - Hsiung-Ying Huang
- Department of Pulmonary and Critical Care Medicine, Xiamen Chang Gung Hospital, Xiamen, Fujian, China
| | - Wen-Cheng Li
- Department of Family Medicine, Chang Gung Memorial Hospital Linkou Main Branch, Taoyuan, Taiwan
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Department of Health Management, Xiamen Chang Gung Hospital, Xiamen, Fujian, China
| | - Jau-Yuan Chen
- Department of Family Medicine, Chang Gung Memorial Hospital Linkou Main Branch, Taoyuan, Taiwan
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
| |
Collapse
|
|
12
|
Yoo JH, Choi MS, Ahn J, Park SW, Kim Y, Hur KY, Jin SM, Kim G, Kim JH. Association Between Continuous Glucose Monitoring-Derived Time in Range, Other Core Metrics, and Albuminuria in Type 2 Diabetes. Diabetes Technol Ther 2020; 22:768-776. [PMID: 32167394 DOI: 10.1089/dia.2019.0499] [Citation(s) in RCA: 67] [Impact Index Per Article: 13.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Background: As the use of continuous glucose monitoring (CGM) has increased, time in range (TIR) and other core CGM metrics are now emerging as the core metrics for clinical targets and assessing diabetic complications, beyond HbA1c. This study investigated the association between the CGM-derived TIR, hyperglycemia, hypoglycemia metrics, and albuminuria. Methods: A total of 866 subjects with type 2 diabetes who underwent 3 or 6 days of CGM and had urinary albumin-to-creatinine ratio (ACR) measurements were retrospectively reviewed. CGM metrics were defined according to the most recent international consensus. Albuminuria was defined as one or more of the ACR measurements being >30 mg/g. Results: The overall prevalence of albuminuria was 36.6%. The prevalence of albuminuria was lower in subjects who achieved the target of TIR 70-180 mg/dL, time above range (TAR) >180 mg/dL, and TAR >250 mg/dL, as recommended by international consensus (P < 0.001). Multiple logistic regression analysis revealed that the odds ratio of having albuminuria was 0.94 (95% confidence interval: 0.88-0.99, P for trend = 0.04) per 10% increase in TIR of 70-180 mg/dL, after adjusting for multiple factors, including glycemic variability. The results were similar for hyperglycemia metrics (TAR >250 mg/dL and TAR >180 mg/dL). Conclusions: TIR 70-180 mg/dL and hyperglycemia metrics are strongly associated with albuminuria in type 2 diabetes.
Collapse
Affiliation(s)
- Jee Hee Yoo
- Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea
| | - Min Sun Choi
- Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Jiyeon Ahn
- Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Sung Woon Park
- Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Yejin Kim
- Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Kyu Yeon Hur
- Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Sang-Man Jin
- Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Gyuri Kim
- Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Jae Hyeon Kim
- Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| |
Collapse
|
|
13
|
Liu L, Xia R, Song X, Zhang B, He W, Zhou X, Li S, Yuan G. Association between the triglyceride-glucose index and diabetic nephropathy in patients with type 2 diabetes: A cross-sectional study. J Diabetes Investig 2020; 12:557-565. [PMID: 33319507 PMCID: PMC8015837 DOI: 10.1111/jdi.13371] [Citation(s) in RCA: 49] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2020] [Revised: 06/27/2020] [Accepted: 07/17/2020] [Indexed: 12/12/2022] Open
Abstract
Aims/Introduction The triglyceride–glucose (TyG) index has been proposed as a reliable and simple marker of insulin resistance. We investigated the association between TyG index and diabetic nephropathy (DN) in patients with type 2 diabetes. Materials and Methods A consecutive case series of 682 adult patients with type 2 diabetes hospitalized in the Department of Endocrinology at the Tongji Hospital (Wuhan, Hubei, China) from January 2007 to December 2009 was included in this cross‐sectional analysis. Receiver operating characteristics curve analysis, correlation analysis and multiple logistic regression analysis were carried out. Results A total of 232 (34.0%) participants were identified with DN. Compared with the non‐DN group, the DN group had longer disease duration, and higher bodyweight, systolic blood pressure, diastolic blood pressure, glycated hemoglobin, triglycerides, total cholesterol, serum uric acid, 24 h‐urinary albumin, TyG index and homeostasis model assessment 2 estimates for insulin resistance (HOMA2‐IR; P < 0.05 for each). The TyG index with an optimal cut‐off point >9.66 showed a higher area under the receiver operating characteristic curve of 0.67 (P = 0.002) than HOMA2‐IR (area under the curve 0.61, P = 0.029) on receiver operating characteristic curve analysis for DN identification. Additionally, the TyG index positively correlated with the levels of metabolic indicators (bodyweight, glycated hemoglobin, triglycerides, total cholesterol, serum uric acid, fasting glucose and HOMA2‐IR) and natural logarithmic 24 h‐urinary albumin (P < 0.05 for each), but not natural logarithm of estimated glomerular filtration rate. On multiple regression analysis, an increased TyG index was shown to be an independent risk factor (odds ratio 1.91, P = 0.001) for DN. Conclusions The TyG index was independently associated with DN in patients with type 2 diabetes, and was a better marker than HOMA2‐IR for identification of DN in type 2 diabetes patients.
Collapse
Affiliation(s)
- Li Liu
- Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Rui Xia
- Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Xiaoqing Song
- Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Benping Zhang
- Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Wentao He
- Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Xinrong Zhou
- Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Shengzhong Li
- Department of Surgery, Wuhan Jinyintan Hospital, Wuhan, Hubei, China
| | - Gang Yuan
- Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| |
Collapse
|
|
14
|
Wang A, Zhang J, Li J, Li H, Zuo Y, Lv W, Chen S, Li J, Meng X, Wu S, Zhao X, Wang Y. Relationship Between Time-Dependent Proteinuria and Risk of Stroke in Population With Different Glucose Tolerance Status. J Am Heart Assoc 2020; 9:e015776. [PMID: 32536236 PMCID: PMC7670539 DOI: 10.1161/jaha.120.015776] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
Background Proteinuria often changes and is known as a “time‐dependent exposure.” The effect of time‐dependent proteinuria on the risk of future stroke remains unclear. Proteinuria is often detected in patients with diabetes mellitus. The present study was designed to evaluate the association between time‐dependent proteinuria and the risk of stroke in a patient cohort with different glucose tolerance status. Methods and Results A total of 82 938 participants, who were free of myocardial infarction or stroke and underwent fasting blood glucose and urinary protein measurements at baseline in the Kailuan study, were enrolled. Proteinuria was determined using urine dipstick tests at baseline and subsequent follow‐ups. Time‐dependent proteinuria was defined as the status of urine protein updated through the follow‐up examinations, separately. Time‐dependent Cox regression models were used to analyze the relationship between time‐dependent proteinuria and the risk of stroke. During a median follow‐up of 8.37 years, 2538 participants developed stroke. After adjusting for confounding factors, the hazard ratio (95% CI) for stroke in time‐dependent proteinuria among all participants, and the normoglycemia, prediabetes, and diabetes mellitus populations were 1.68 (1.49–1.89), 1.73 (1.47–2.05), 2.15 (1.70–2.72), and 1.30 (1.03–1.65), respectively. There were interaction effects in patients with normoglycemia and prediabetes compared with those with diabetes mellitus. Findings were similar for ischemic and hemorrhagic strokes and were confirmed in sensitivity analyses. Conclusions Time‐dependent proteinuria is an independent risk factor of stroke, especially in the normoglycemia and prediabetes populations.
Collapse
Affiliation(s)
- Anxin Wang
- China National Clinical Research Center for Neurological Diseases Beijing Tiantan Hospital Capital Medical University Beijing China.,Department of Neurology Beijing Tiantan Hospital Capital Medical University Beijing China
| | - Jia Zhang
- China National Clinical Research Center for Neurological Diseases Beijing Tiantan Hospital Capital Medical University Beijing China.,Department of Neurology Beijing Tiantan Hospital Capital Medical University Beijing China
| | - Jingjing Li
- Department of Neurology Yangquan Coalmine Group General Hospital Yangquan China
| | - Haibin Li
- School of Public Health Capital Medical University Beijing China
| | - Yingting Zuo
- China National Clinical Research Center for Neurological Diseases Beijing Tiantan Hospital Capital Medical University Beijing China.,Department of Neurology Beijing Tiantan Hospital Capital Medical University Beijing China
| | - Wei Lv
- China National Clinical Research Center for Neurological Diseases Beijing Tiantan Hospital Capital Medical University Beijing China.,Department of Neurology Beijing Tiantan Hospital Capital Medical University Beijing China
| | - Shuohua Chen
- Department of Cardiology Kailuan Hospital North China University of Science and Technology Tangshan China
| | - Junjuan Li
- Department of Nephrology Kailuan Hospital North China University of Science and Technology Tangshan China
| | - Xia Meng
- China National Clinical Research Center for Neurological Diseases Beijing Tiantan Hospital Capital Medical University Beijing China.,Department of Neurology Beijing Tiantan Hospital Capital Medical University Beijing China
| | - Shouling Wu
- Department of Cardiology Kailuan Hospital North China University of Science and Technology Tangshan China
| | - Xingquan Zhao
- China National Clinical Research Center for Neurological Diseases Beijing Tiantan Hospital Capital Medical University Beijing China.,Department of Neurology Beijing Tiantan Hospital Capital Medical University Beijing China
| | - Yongjun Wang
- China National Clinical Research Center for Neurological Diseases Beijing Tiantan Hospital Capital Medical University Beijing China.,Department of Neurology Beijing Tiantan Hospital Capital Medical University Beijing China
| |
Collapse
|
|
15
|
PPARG Pro12Ala Polymorphism with CKD in Asians: A Meta-Analysis Combined with a Case-Control Study-A Key for Reaching Null Association. Genes (Basel) 2020; 11:genes11060705. [PMID: 32604723 PMCID: PMC7349649 DOI: 10.3390/genes11060705] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2020] [Revised: 06/20/2020] [Accepted: 06/23/2020] [Indexed: 11/17/2022] Open
Abstract
BACKGROUND So far, numerous meta-analyses have been published regarding the correlation between peroxisome proliferator-activated receptor gamma (PPARG) proline 12 alanine (Pro12Ala) gene polymorphism and chronic kidney disease (CKD); however, the results appear to be contradictory. Hence, this study is formulated with the objective of using existing meta-analysis data together with our research population to study the correlation between PPARG Pro12Ala gene polymorphism and CKD and evaluate whether an accurate result can be obtained. METHODS First, literature related to CKD and PPARG Pro12Ala available on the PubMed and EMBASE databases up to December 2016 was gathered from 20 publications. Then, the gathered results were combined with our case-control study of 1693 enrolled subjects and a trial sequential analysis (TSA) was performed to verify existing evidence and determine whether a firm conclusion can be drawn. RESULTS The TSA results showed that the cumulative sample size for the Asian sample was 6078 and was sufficient to support a definite result. The results of this study confirmed that there is no obvious correlation between PPARG Pro12Ala and CKD for Asians (OR = 0.82 (95% CI = 0.66-1.02), I2 = 63.1%), but this was not confirmed for Caucasians. Furthermore, the case-control sample in our study was shown to be the key for reaching this conclusion. CONCLUSIONS The meta-analysis results of this study suggest no significant correlation between PPARG Pro12Ala gene polymorphism and CKD for Asians after adding our samples, but not for Caucasian.
Collapse
|
|
16
|
Effects of low skeletal muscle mass and sarcopenic obesity on albuminuria: a 7-year longitudinal study. Sci Rep 2020; 10:5774. [PMID: 32238873 PMCID: PMC7113302 DOI: 10.1038/s41598-020-62841-y] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2019] [Accepted: 03/19/2020] [Indexed: 12/25/2022] Open
Abstract
We aimed to identify the association between low skeletal muscle, sarcopenic obesity, and the incidence of albuminuria in the general population using a longitudinal study. Data from 29,942 subjects who underwent two or more routine health examinations from 2006 to 2013 were retrospectively reviewed. Relative skeletal muscle mass was presented using the skeletal muscle mass index (SMI), a measure of body weight-adjusted appendicular skeletal muscle mass estimated by bioelectrical impedance analysis. The cumulative incidence of albuminuria was 981 (3.3%) during the 7-year follow-up period. The hazard ratio of incident albuminuria was 1.44 (95% CI: 1.22–1.71, p for trend <0.001) in the lowest SMI tertile relative to the highest SMI tertile after multivariable adjustment. After additionally adjusting for general and central obesity, the hazard ratio was 1.35 (95% CI: 1.13–1.61, p for trend = 0.001) and 1.30 (95% CI: 1.08–1.56, p for trend = 0.003), respectively. Furthermore, the risk of developing albuminuria was much higher in the sarcopenic obesity group (HR: 1.49, 95% CI: 1.21–1.81, p for trend <0.001) compared to the other groups. Sarcopenic obesity, as well as low skeletal muscle, may lead to albuminuria in general populations.
Collapse
|
|
17
|
Yilmaz PD, Kadiyoran C. The Relationship between Microalbuminuria and Atherosclerosis in Patients with Type II Diabetes and Evaluate the Parameters of Internal Carotid Artery Duplex Sonographic Scanning. JOURNAL OF MEDICAL SCIENCES AND HEALTH 2019. [DOI: 10.46347/jmsh.2019.v05i01.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022] Open
|
|
18
|
Nickel NP, de Jesus Perez VA, Zamanian RT, Fessel JP, Cogan JD, Hamid R, West JD, de Caestecker MP, Yang H, Austin ED. Low-grade albuminuria in pulmonary arterial hypertension. Pulm Circ 2019; 9:2045894018824564. [PMID: 30632900 PMCID: PMC6557031 DOI: 10.1177/2045894018824564] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Low-grade albuminuria, determined by the urinary albumin to creatinine ratio, has been linked to systemic vascular dysfunction and is associated with cardiovascular mortality. Pulmonary arterial hypertension is related to mutations in the bone morphogenetic protein receptor type 2, pulmonary vascular dysfunction and is increasingly recognized as a systemic disease. In a total of 283 patients (two independent cohorts) diagnosed with pulmonary arterial hypertension, 18 unaffected BMPR2 mutation carriers and 68 healthy controls, spot urinary albumin to creatinine ratio and its relationship to demographic, functional, hemodynamic and outcome data were analyzed. Pulmonary arterial hypertension patients and unaffected BMPR2 mutation carriers had significantly elevated urinary albumin to creatinine ratios compared with healthy controls ( P < 0.01; P = 0.04). In pulmonary arterial hypertension patients, the urinary albumin to creatinine ratio was associated with older age, lower six-minute walking distance, elevated levels of C-reactive protein and hemoglobin A1c, but there was no correlation between the urinary albumin to creatinine ratio and hemodynamic variables. Pulmonary arterial hypertension patients with a urinary albumin to creatinine ratio above 10 µg/mg had significantly higher rates of poor outcome ( P < 0.001). This study shows that low-grade albuminuria is prevalent in pulmonary arterial hypertension patients and is associated with poor outcome. This study shows that albuminuria in pulmonary arterial hypertension is associated with systemic inflammation and insulin resistance.
Collapse
Affiliation(s)
- Nils P Nickel
- 1 Stanford University School of Medicine, Stanford University, USA.,2 Vanderbilt University Medical Center, USA
| | | | - Roham T Zamanian
- 1 Stanford University School of Medicine, Stanford University, USA
| | | | | | | | | | | | | | | |
Collapse
|
|
19
|
Sattarinezhad A, Roozbeh J, Shirazi Yeganeh B, Omrani G, Shams M. Resveratrol reduces albuminuria in diabetic nephropathy: A randomized double-blind placebo-controlled clinical trial. DIABETES & METABOLISM 2019; 45:53-59. [DOI: 10.1016/j.diabet.2018.05.010] [Citation(s) in RCA: 88] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/02/2018] [Revised: 05/18/2018] [Accepted: 05/27/2018] [Indexed: 02/04/2023]
|
|
20
|
Das G, Taylor PN, Abusahmin H, Ali A, Tennant BP, Geen J, Okosieme O. Relationship between serum thyrotropin and urine albumin excretion in euthyroid subjects with diabetes. Ann Clin Biochem 2018; 56:155-162. [PMID: 30114929 DOI: 10.1177/0004563218797979] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
BACKGROUND Microalbuminuria represents vascular and endothelial dysfunction. Thyroid hormones can influence urine albumin excretion as it exerts crucial effects on the kidney and on the vascular system. This study explores the relationship between serum thyrotropin and urine albumin excretion in euthyroid patients with diabetes. METHODS A total of 433 patients with type 1 or 2 diabetes were included in this retrospective cross-sectional study. Data included anthropometric measurements and biochemical parameters from diabetes clinic. Males with urine albumin creatinine ratio >2.5 and female's >3.5 mg/mmoL were considered to have microalbuminuria. RESULTS 34.9% of the patients had microalbuminuria. Prevalence of microalbuminuria increased according to TSH quartiles (26.9, 34.6, 38.5 and 44.9%, P for trend = 0.02). In a fully adjusted logistic regression model, higher TSH concentrations were associated with high prevalence of microalbuminuria (adjusted odds ratio 2.06 [95% CI: 1.14-3.72]; P = 0.02), while comparing the highest with the lowest quartile of TSH. Multiple linear regression analysis showed an independent association between serum TSH and urine albumin creatinine ratio (β = 0.007, t = 2.03 and P = 0.04). The risk of having microalbuminuria was higher with rise in TSH concentration in patients with younger age (<65 years), raised body mass index (≥25 kg/m2), hypertension, type 2 diabetes and hyperlipidaemia and age was the most important determinant ( P for interaction = 0.02). CONCLUSION Serum TSH even in the euthyroid range was positively associated with microalbuminuria in euthyroid patients with diabetes independent of traditional risk factors. This relationship was strongest in patients with components of the metabolic syndrome.
Collapse
Affiliation(s)
- Gautam Das
- 1 Department of Endocrinology, Prince Charles Hospital, Cwm Taf University Health Board, Merthyr Tydfil, UK
| | - Peter N Taylor
- 2 Department of Endocrinology, University Hospital of Wales, Cardiff and Vale University Health Board, Cardiff, UK.,3 Thyroid Research Group, Systems Immunity Research Institute, Cardiff University School of Medicine, Cardiff, UK
| | - Hussam Abusahmin
- 1 Department of Endocrinology, Prince Charles Hospital, Cwm Taf University Health Board, Merthyr Tydfil, UK
| | - Amer Ali
- 1 Department of Endocrinology, Prince Charles Hospital, Cwm Taf University Health Board, Merthyr Tydfil, UK
| | - Brian P Tennant
- 4 Department of Clinical Biochemistry, Prince Charles Hospital, Cwm Taf University Health Board, Merthyr Tydfil, UK
| | - John Geen
- 4 Department of Clinical Biochemistry, Prince Charles Hospital, Cwm Taf University Health Board, Merthyr Tydfil, UK.,5 Faculty of Life Sciences and Education, University of South Wales, Pontypridd, UK
| | - Onyebuchi Okosieme
- 1 Department of Endocrinology, Prince Charles Hospital, Cwm Taf University Health Board, Merthyr Tydfil, UK.,3 Thyroid Research Group, Systems Immunity Research Institute, Cardiff University School of Medicine, Cardiff, UK
| |
Collapse
|
|
21
|
Prudente S, Di Paola R, Copetti M, Lucchesi D, Lamacchia O, Pezzilli S, Mercuri L, Alberico F, Giusti L, Garofolo M, Penno G, Cignarelli M, De Cosmo S, Trischitta V. The rs12917707 polymorphism at the UMOD locus and glomerular filtration rate in individuals with type 2 diabetes: evidence of heterogeneity across two different European populations. Nephrol Dial Transplant 2018; 32:1718-1722. [PMID: 27448670 DOI: 10.1093/ndt/gfw262] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2016] [Accepted: 06/04/2016] [Indexed: 11/12/2022] Open
Abstract
Background UMOD variability has been associated at a genome-wide level of statistical significance with glomerular filtration rate (GFR) in Swedish individuals with type 2 diabetes (T2D; n = 4888). Whether this finding is extensible also to diabetic patients from other populations deserves further study. Our aim was to investigate the relationship between UMOD variability and GFR in patients with T2D from Italy. Methods Genotyping of the single nucleotide polymorphism (SNP) rs12917707 at the UMOD locus has been carried out in 3087 individuals from four independent Italian cohorts of patients with T2D by TaqMan allele discrimination. Results In none of the four study cohorts was rs12917707 significantly associated with GFR (P > 0.05 for all). Similar results were obtained when the four samples were pooled and analyzed together (β = 0.83, P = 0.19). Such effect was strikingly smaller than that previously reported in Swedish patients (P for heterogeneity = 1.21 × 10-7). Conclusions The previously reported strong association between rs12917707 and GFR in diabetic patients from Sweden is not observed in Italian diabetic patients, thus clearly pointing to a heterogeneous effect across the two different samples. This suggests that UMOD is a strong genetic determinant of kidney function in patients with T2D in some, but not all, populations.
Collapse
Affiliation(s)
- Sabrina Prudente
- Mendel Laboratory, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy
| | - Rosa Di Paola
- Research Unit of Diabetes and Endocrine Diseases, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy
| | - Massimiliano Copetti
- Unit of Biostatistics, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy
| | - Daniela Lucchesi
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Olga Lamacchia
- Unit of Endocrinology, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy
| | - Serena Pezzilli
- Mendel Laboratory, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.,Department of Experimental Medicine, 'Sapienza' University, Rome, Italy
| | - Luana Mercuri
- Mendel Laboratory, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy
| | - Federica Alberico
- Mendel Laboratory, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy
| | - Laura Giusti
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Monia Garofolo
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Giuseppe Penno
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Mauro Cignarelli
- Unit of Endocrinology, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy
| | - Salvatore De Cosmo
- Department of Medical Sciences, IRCCS Casa Sollievo Della Sofferenza, San Giovanni Rotondo, Italy
| | - Vincenzo Trischitta
- Mendel Laboratory, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.,Research Unit of Diabetes and Endocrine Diseases, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.,Department of Experimental Medicine, 'Sapienza' University, Rome, Italy
| |
Collapse
|
|
22
|
Bjornstad P, Nehus E, El Ghormli L, Bacha F, Libman IM, McKay S, Willi SM, Laffel L, Arslanian S, Nadeau KJ. Insulin Sensitivity and Diabetic Kidney Disease in Children and Adolescents With Type 2 Diabetes: An Observational Analysis of Data From the TODAY Clinical Trial. Am J Kidney Dis 2017; 71:65-74. [PMID: 29157731 DOI: 10.1053/j.ajkd.2017.07.015] [Citation(s) in RCA: 58] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2017] [Accepted: 07/25/2017] [Indexed: 12/17/2022]
Abstract
BACKGROUND Diabetic kidney disease is a major cause of premature mortality in type 2 diabetes mellitus (T2DM). Worsening insulin sensitivity independent of glycemic control may contribute to the development of diabetic kidney disease. We investigated the longitudinal association of insulin sensitivity with hyperfiltration and increased albumin excretion in adolescents with T2DM. STUDY DESIGN Observational prospective cohort study. SETTING & PARTICIPANTS 532 TODAY (Treatment Options for Type 2 Diabetes in Adolescents and Youth) participants aged 12 to 17 years with T2DM duration less than 2 years at baseline. The TODAY Study was a multicenter randomized clinical trial that examined the efficacy of 3 treatment regimens (metformin monotherapy, metformin plus rosiglitazone, or metformin plus an intensive lifestyle intervention program) to achieve durable glycemic control. PREDICTORS Natural log-transformed estimated insulin sensitivity (reciprocal of fasting insulin), hemoglobin A1c concentration, age, race-ethnicity, treatment group, body mass index, loss of glycemic control, and hypertension. OUTCOMES Hyperfiltration was defined as 99th percentile or higher of estimated glomerular filtration rate (≥140mL/min/1.73m2) when referenced to healthy adolescents (NHANES 1999-2002) and albumin-creatinine ratio ≥ 30μg/mg at 3 consecutive annual visits. RESULTS Hyperfiltration was observed in 7.0% of participants at baseline and in 13.3% by 5 years, with a cumulative incidence of 5.0% over 5 years. The prevalence of increased albumin excretion was 6% at baseline and 18% by 5 years, with a cumulative incidence of 13.4%. There was an 8% increase in risk for hyperfiltration per 10% lower estimated insulin sensitivity in unadjusted and adjusted models (P=0.01). Increased albumin excretion was associated with hemoglobin A1c concentration, but not estimated insulin sensitivity. LIMITATIONS Longer follow-up is needed to capture the transition from hyperfiltration to rapid glomerular filtration rate decline in youth-onset T2DM. CONCLUSIONS Lower estimated insulin sensitivity was associated with risk for hyperfiltration over time, whereas increased albumin excretion was associated with hyperglycemia in youth-onset T2DM.
Collapse
Affiliation(s)
- Petter Bjornstad
- University of Colorado Anschutz Medical Campus and Children's Hospital Colorado, Aurora, CO
| | - Edward Nehus
- Cincinnati Children's Hospital Medical Center, Cincinnati, OH
| | - Laure El Ghormli
- George Washington University Biostatistics Center, Rockville, MD.
| | - Fida Bacha
- Texas Children's Hospital, Baylor College of Medicine, Houston, TX
| | - Ingrid M Libman
- Children's Hospital University of Pittsburgh Medical Center, Pittsburgh, PA
| | | | - Steven M Willi
- Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA
| | | | - Silva Arslanian
- Children's Hospital University of Pittsburgh Medical Center, Pittsburgh, PA
| | - Kristen J Nadeau
- University of Colorado Anschutz Medical Campus and Children's Hospital Colorado, Aurora, CO
| | | |
Collapse
|
|
23
|
Wang A, Jiang R, Su Z, Zhang J, Zhao X, Wu S, Guo X. Association of Persistent, Incident, and Remittent Proteinuria With Stroke Risk in Patients With Diabetes Mellitus or Prediabetes Mellitus. J Am Heart Assoc 2017; 6:e006178. [PMID: 29025745 PMCID: PMC5721839 DOI: 10.1161/jaha.117.006178] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2017] [Accepted: 08/14/2017] [Indexed: 11/30/2022]
Abstract
BACKGROUND Proteinuria often changes dynamically, showing either regression or progression. The impact of changes in proteinuria on future stroke risk remains largely unknown. We hypothesized that changes in proteinuria would be associated with stroke risk in patients with diabetes mellitus and prediabetes mellitus. METHODS AND RESULTS The study population included 17 380 participants with diabetes mellitus or prediabetes mellitus enrolled in a prospective Chinese cohort. From the baseline and 2-year dipstick screening results, participants were classified as having no proteinuria or remittent, incident, or persistent proteinuria. Reduction in proteinuria was calculated as the baseline minus 2-year proteinuria. Stroke outcomes were assessed in subsequent follow-ups. Data were analyzed using Cox proportional-hazards models. During a median follow-up of 6.9 years, we identified 751 patients with stroke. Stroke risk was increased for participants with persistent (hazard ratio [HR], 1.64; 95% confidence interval [CI], 1.18-2.30), incident (HR, 1.52; 95% CI, 1.22-1.89), and remittent (HR, 1.42; 95% CI, 1.01-2.02) proteinuria compared with those with no proteinuria. Persistent proteinuria was associated with a higher risk of stroke for participants with prediabetes mellitus (HR, 2.58; 95% CI, 1.58-4.22) compared with those with diabetes mellitus (HR, 1.35; 95% CI, 0.86-2.12 [P for interaction=0.0083]). Proteinuria reduction contributed to a decrease in stroke incidence (HR, 0.88; 95% CI, 0.81-0.95). The results were confirmed by sensitivity analyses. CONCLUSIONS Persistent, incident, and remittent proteinuria are independent indicators of stroke risk in both diabetic and prediabetic populations.
Collapse
Affiliation(s)
- Anxin Wang
- Department of Epidemiology and Health Statistics, School of Public Health, Capital Medical University, Beijing, China
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
- China National Clinical Research Center for Neurological Diseases, Beijing, China
- Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China
- Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China
- Beijing Municipal Key Laboratory of Clinical Epidemiology, Beijing, China
| | - Ruixuan Jiang
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
- China National Clinical Research Center for Neurological Diseases, Beijing, China
- Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China
- Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China
| | - Zhaoping Su
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
- China National Clinical Research Center for Neurological Diseases, Beijing, China
- Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China
- Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China
| | - Jia Zhang
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
- China National Clinical Research Center for Neurological Diseases, Beijing, China
- Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China
- Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China
| | - Xingquan Zhao
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
- China National Clinical Research Center for Neurological Diseases, Beijing, China
- Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China
- Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China
| | - Shouling Wu
- Department of Cardiology, Kailuan Hospital, North China University of Science and Technology, Tangshan, China
| | - Xiuhua Guo
- Department of Epidemiology and Health Statistics, School of Public Health, Capital Medical University, Beijing, China
- Beijing Municipal Key Laboratory of Clinical Epidemiology, Beijing, China
| |
Collapse
|
|
24
|
Yoon HE, Nam Y, Kang E, Hwang HS, Shin SJ, Hong YS, Kang KY. Gender-Specific Associations between Low Skeletal Muscle Mass and Albuminuria in the Middle-Aged and Elderly Population. Int J Med Sci 2017; 14:1054-1064. [PMID: 29104458 PMCID: PMC5666535 DOI: 10.7150/ijms.20286] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2017] [Accepted: 07/24/2017] [Indexed: 12/21/2022] Open
Abstract
Objective This study assessed gender-specific associations between low muscle mass (LMM) and albuminuria. Methods Data from the Korea National Health and Nutrition Examination Survey 2011 were employed. The study consisted of 1,087 subjects (≥50 years old). Skeletal muscle index (SMI) was defined as the weight-adjusted appendicular skeletal muscle mass. Mild LMM and severe LMM were defined as SMI that were 1-2 and >2 standard deviations below the sex-specific mean appendicular skeletal muscle mass of young adults, respectively. Increased albuminuria was defined as albumin-to-creatinine ratio ≥30mg/g Results Men with mild and severe LMM were significantly more likely to have increased albuminuria (15.2% and 45.45%, respectively) than men with normal SMI (9.86%, P<0.0001), but not women. Severe LMM associated independently with increased albuminuria in men (OR=7.661, 95% CI=2.72-21.579) but not women. Severe LMM was an independent predictor of increased albuminuria in hypertensive males (OR=11.449, 95% CI=3.037-43.156), non-diabetic males (OR=8.782, 95% CI=3.046-25.322), and males without metabolic syndrome (MetS) (OR=8.183, 95% CI=1.539-43.156). This was not observed in males without hypertension, males with diabetes or MetS, and all female subgroups. Conclusion Severe LMM associated with increased albuminuria in men, especially those with hypertension and without diabetes or MetS.
Collapse
Affiliation(s)
- Hye Eun Yoon
- Division of Nephrology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea.,Department of Internal Medicine, Incheon St. Mary's Hospital
| | - Yunju Nam
- Division of Nephrology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea.,Department of Internal Medicine, Incheon St. Mary's Hospital
| | - Eunjin Kang
- Division of Nephrology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea.,Department of Internal Medicine, Incheon St. Mary's Hospital
| | - Hyeon Seok Hwang
- Division of Nephrology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea.,Department of Internal Medicine, Daejeon St. Mary's Hospital
| | - Seok Joon Shin
- Division of Nephrology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea.,Department of Internal Medicine, Incheon St. Mary's Hospital
| | - Yeon Sik Hong
- Department of Internal Medicine, Incheon St. Mary's Hospital.,Division of Rheumatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea
| | - Kwi Young Kang
- Department of Internal Medicine, Incheon St. Mary's Hospital.,Division of Rheumatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea
| |
Collapse
|
|
25
|
Østergaard MV, Pinto V, Stevenson K, Worm J, Fink LN, Coward RJM. DBA2J db/db mice are susceptible to early albuminuria and glomerulosclerosis that correlate with systemic insulin resistance. Am J Physiol Renal Physiol 2016; 312:F312-F321. [PMID: 27852608 DOI: 10.1152/ajprenal.00451.2016] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2016] [Revised: 10/26/2016] [Accepted: 11/09/2016] [Indexed: 12/12/2022] Open
Abstract
Diabetic nephropathy (DN) is the leading cause of kidney failure in the world. To understand important mechanisms underlying this condition, and to develop new therapies, good animal models are required. In mouse models of type 1 diabetes, the DBA/2J strain has been shown to be more susceptible to develop kidney disease than other common strains. We hypothesized this would also be the case in type 2 diabetes. We studied db/db and wild-type (wt) DBA/2J mice and compared these with the db/db BLKS/J mouse, which is currently the most widely used type 2 DN model. Mice were analyzed from age 6 to 12 wk for systemic insulin resistance, albuminuria, and glomerular histopathological and ultrastructural changes. Body weight and nonfasted blood glucose were increased by 8 wk in both genders, while systemic insulin resistance commenced by 6 wk in female and 8 wk in male db/db DBA/2J mice. The urinary albumin-to-creatinine ratio (ACR) was closely linked to systemic insulin resistance in both sexes and was increased ~50-fold by 12 wk of age in the db/db DBA/2J cohort. Glomerulosclerosis, foot process effacement, and glomerular basement membrane thickening were observed at 12 wk of age in db/db DBA/2J mice. Compared with db/db BLKS/J mice, db/db DBA/2J mice had significantly increased levels of urinary ACR, but similar glomerular histopathological and ultrastructural changes. The db/db DBA/2J mouse is a robust model of early-stage albuminuric DN, and its levels of albuminuria correlate closely with systemic insulin resistance. This mouse model will be helpful in defining early mechanisms of DN and ultimately the development of novel therapies.
Collapse
Affiliation(s)
- Mette V Østergaard
- Global Research, Novo Nordisk, Måløv, Denmark.,Bristol Renal, School of Clinical Sciences, University of Bristol, Bristol, United Kingdom; and
| | - Vanda Pinto
- Bristol Renal, School of Clinical Sciences, University of Bristol, Bristol, United Kingdom; and
| | - Kirsty Stevenson
- Department of Biochemistry, Bristol Royal Infirmary, Bristol, United Kingdom
| | - Jesper Worm
- Global Research, Novo Nordisk, Måløv, Denmark
| | | | - Richard J M Coward
- Bristol Renal, School of Clinical Sciences, University of Bristol, Bristol, United Kingdom; and
| |
Collapse
|
|
26
|
Mottl AK, Divers J, Dabelea D, Maahs DM, Dolan L, Pettitt D, Marcovina S, Imperatore G, Pihoker C, Mauer M, Mayer-Davis EJ. The dose-response effect of insulin sensitivity on albuminuria in children according to diabetes type. Pediatr Nephrol 2016; 31:933-40. [PMID: 26754041 PMCID: PMC4841707 DOI: 10.1007/s00467-015-3276-2] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2015] [Revised: 10/25/2015] [Accepted: 10/26/2015] [Indexed: 12/17/2022]
Abstract
BACKGROUND Insulin resistance is associated with microalbuminuria among youth with diabetes mellitus. We sought to determine the dose-response effect of insulin sensitivity (IS) on the magnitude of albuminuria and whether there is a threshold below which urine albumin excretion increases. METHODS These analyses included participants from the SEARCH for Diabetes in Youth Study with incident diabetes who completed a baseline study visit (n = 2988). We estimated IS using a validated equation incorporating waist circumference, HbA1C, and fasting serum triglycerides. Multivariate regression analyses were performed to assess the effect of IS on urine albumin creatinine ratio (UACR), stratified by diabetes type. The IS threshold was then determined using segmented regressions within each diabetes type and incorporated into the multivariate model. RESULTS There was an association between IS and UACR in type 2 diabetes only (beta = -0.39; p < 0.001). There was strong statistical evidence for a threshold effect of IS score on UACR in the group of youth with type 2 (beta = 0.40; p < 0.001) but not type 1 diabetes (p = 0.3). CONCLUSIONS In cross-sectional analyses, there is a negative association between IS and UACR in youth with type 2 but not type 1 diabetes, and this association likely includes a threshold effect of IS on UACR.
Collapse
Affiliation(s)
- Amy K Mottl
- UNC Division of Nephrology and Hypertension, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
| | - Jasmin Divers
- Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA
| | - Dana Dabelea
- Department of Epidemiology, School of Public Health, University of Colorado Denver, Aurora, CO, USA
| | - David M Maahs
- Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Aurora, CO, USA
| | - Lawrence Dolan
- Division of Endocrinology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
| | | | - Santica Marcovina
- Northwest Lipid Metabolism and Diabetes Research Laboratories, Department of Medicine, University of Washington, Seattle, WA, USA
| | - Giuseppina Imperatore
- Division of Diabetes Translation, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - Catherine Pihoker
- Department of Pediatrics, University of Washington, Seattle, WA, USA
| | - Michael Mauer
- Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN, USA
- Department of Medicine, University of Minnesota Medical School, Minneapolis, MN, USA
| | - Elizabeth J Mayer-Davis
- Department of Nutrition, University of North Carolina School of Public Health, Chapel Hill, NC, USA
- Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, USA
| |
Collapse
|
|
27
|
Bjornstad P, Cherney DZ, Maahs DM, Nadeau KJ. Diabetic Kidney Disease in Adolescents With Type 2 Diabetes: New Insights and Potential Therapies. Curr Diab Rep 2016; 16:11. [PMID: 26803647 PMCID: PMC5841446 DOI: 10.1007/s11892-015-0708-0] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease (ESRD) and dialysis in the Western world. Early DKD, including microalbuminuria and renal hyperfiltration, is common in adolescents with type 2 diabetes (T2D). Furthermore, youth-onset T2D carries a higher risk of progressive DKD than adult-onset T2D of similar diabetes duration. DKD is characterized by a long clinically silent period without signs of disease. Therefore, a major challenge in preventing DKD is the difficulty in identifying high-risk T2D patients at an early stage. The Type 2 Diabetes in Adolescents and Youth (TODAY) study demonstrated a high initial prevalence that increased over time, irrespective of treatment arm. This key observation underscores the importance of discovering new therapeutic targets to supplement conventional management, in order to reduce DKD risk. In this review, we focus on early DKD in T2D and summarize potential novel biomarkers and therapeutic targets.
Collapse
Affiliation(s)
- Petter Bjornstad
- Department of Pediatric Endocrinology, University of Colorado School of Medicine, Aurora, CO, USA.
- Barbara Davis Center for Diabetes, University of Colorado School of Medicine, 13123 East 16th Ave, Box B265, Aurora, CO, 80045, USA.
| | - David Z Cherney
- Department of Medicine, Division of Nephrology, Toronto General Hospital, University of Toronto, Toronto, ON, Canada
| | - David M Maahs
- Department of Pediatric Endocrinology, University of Colorado School of Medicine, Aurora, CO, USA
- Barbara Davis Center for Diabetes, University of Colorado School of Medicine, 13123 East 16th Ave, Box B265, Aurora, CO, 80045, USA
- Department of Medicine, Division of Nephrology, University of Colorado, Aurora, CO, USA
| | - Kristen J Nadeau
- Department of Pediatric Endocrinology, University of Colorado School of Medicine, Aurora, CO, USA
- Barbara Davis Center for Diabetes, University of Colorado School of Medicine, 13123 East 16th Ave, Box B265, Aurora, CO, 80045, USA
| |
Collapse
|
|
28
|
Affiliation(s)
| | - Amy K Mottl
- University of North Carolina, Chapel Hill, NC
| |
Collapse
|
|
29
|
Park SK, Chun H, Ryoo JH, Lee SW, Lee HS, Shim KW, Cho CY, Ryu DR, Ko TS, Kim E, Park SJ, Park JH, Hong SJ, Hong HP. A cohort study of incident microalbuminuria in relation to HOMA-IR in Korean men. Clin Chim Acta 2015; 446:111-6. [PMID: 25896961 DOI: 10.1016/j.cca.2015.03.043] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2015] [Revised: 03/30/2015] [Accepted: 03/30/2015] [Indexed: 11/29/2022]
Abstract
BACKGROUND Despite the previous studies showing the relationship between microalbuminuria and insulin resistance, longitudinal effect of insulin resistance on development of microalbuminuria is not clearly identified in non-diabetic population. METHODS One thousand six hundred three non-diabetic Korean men without microalbuminuria in 2005 had been followed up for the development of microalbuminuria until 2010. Microalbuminuria was evaluated by urine-albumin creatinine ration, and insulin resistance was evaluated by homeostasis model assessment of insulin resistance (HOMA-IR). Cox proportional hazards model was used to estimate the risk for microalbuminuria according to the tertile of HOMA-IR. RESULTS During 5465.8 person-y of average follow-up, microalbuminuria developed in 76 (4.7%) participants. Incidence of microalbuminuria increased in proportion to the level of HOMA-IR (tertile 1: 3.0%, tertile 2: 4.1%, tertile 3: 7.1%, P<0.001). When the 1st tertile of HOMA-IR was set as reference, hazard ratios and 95% confidence interval were 1.15 (0.56-2.35) and 2.07 (1.05-4.09) for those in the 2nd and 3rd tertiles of HOMA-IR, even after adjusting multiple covariates, respectively (P for linear trend=0.054). CONCLUSIONS Increased insulin resistance was a predictor of microalbuminuria in Korean men.
Collapse
Affiliation(s)
- Sung Keun Park
- Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; Department of Preventive Medicine, School of Medicine, Kyung Hee University, Seoul, Republic of Korea
| | - Hyejin Chun
- Health Promotion Center, Ewha Womans University Mokdong Hospital, Ewha Womans University School of Medicine, Seoul, Republic of Korea
| | - Jae-Hong Ryoo
- Department of Preventive Medicine, School of Medicine, Kyung Hee University, Seoul, Republic of Korea.
| | - Sang Wha Lee
- Department of Family Medicine, Ewha Womans University Mokdong Hospital, Ewha Womans University School of Medicine, Seoul, Republic of Korea
| | - Hong Soo Lee
- Department of Family Medicine, Ewha Womans University Mokdong Hospital, Ewha Womans University School of Medicine, Seoul, Republic of Korea
| | - Kyung Won Shim
- Department of Family Medicine, Ewha Womans University Mokdong Hospital, Ewha Womans University School of Medicine, Seoul, Republic of Korea
| | - Choo Yon Cho
- Department of Family Medicine, Soonchunhyang University College of Medicine, Seoul, Republic of Korea
| | - Dong-Ryeol Ryu
- Department of Internal Medicine, Ewha Womans University Mokdong Hospital, Ewha Womans University School of Medicine, Seoul, Republic of Korea
| | - Taeg Su Ko
- Department of Orthopaedic Surgery, Kangbuk Samsung Hospital, Sungkyunkwan University, School of Medicine, Seoul, Republic of Korea
| | - Eugene Kim
- Department of Orthopaedic Surgery, Kangbuk Samsung Hospital, Sungkyunkwan University, School of Medicine, Seoul, Republic of Korea
| | - Se-Jin Park
- Department of Orthopaedic Surgery, Kangbuk Samsung Hospital, Sungkyunkwan University, School of Medicine, Seoul, Republic of Korea
| | - Jai Hyung Park
- Department of Orthopaedic Surgery, Kangbuk Samsung Hospital, Sungkyunkwan University, School of Medicine, Seoul, Republic of Korea
| | - Seok Jin Hong
- Department of Otorhinolaryngology-Head and Neck Surgery, Kangbuk Samsung Hospital, Sungkyunkwan University, School of Medicine, Seoul, Republic of Korea
| | - Hyun Pyo Hong
- Department of Radiology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul 110-746, Republic of Korea
| |
Collapse
|
|
30
|
Jang CM, Hyun YY, Lee KB, Kim H. Insulin resistance is associated with the development of albuminuria in Korean subjects without diabetes. Endocrine 2015; 48:203-10. [PMID: 24676759 DOI: 10.1007/s12020-014-0242-x] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2014] [Accepted: 03/12/2014] [Indexed: 12/13/2022]
Abstract
Previous studies have shown that insulin resistance is associated with the development of albuminuria. However, most studies are done on a background of diabetes or metabolic syndrome and there is little data from general population. The aim of this study is to define the effect of insulin resistance on the development of albuminuria in healthy individuals without diabetes. We analyzed 60,047 participants without baseline diabetes or chronic kidney disease, who underwent at least two health maintenance visits at a 2-year interval between 2002 and 2009 at a tertiary hospital in Korea. We measured the incidence of albuminuria at the second examination and calculated the odds ratio for the development of albuminuria according to the quintile of the homeostasis model assessment of insulin resistance (HOMA-IR). After 2 years, 880 cases of incident albuminuria were observed. The cumulative incidences of albuminuria were 1.08, 1.50, 1.35, 1.47, and 1.92% for the 1st to 5th quintiles of HOMA-IR. On multivariate logistic analysis, the odds ratios for incident albuminuria compared to those in the 1st quintile were 1.38 (95% CI 1.10-1.73; P=0.006), 1.23 (95% CI 0.97-1.55; P=0.087), 1.32 (95% CI 1.04-1.67; P=0.020), and 1.66 (95% CI 1.31-2.09; P<0.001) in the 2nd, 3rd, 4th, and 5th quintiles, respectively. A high level of insulin resistance assessed with HOMA-IR was associated with the development of albuminuria in relatively healthy subjects without diabetes. Further research is needed to verify the role of insulin resistance in the development of albuminuria and renal injury.
Collapse
Affiliation(s)
- Cheol Min Jang
- Department of Internal Medicine, School of Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University, 29 Saemunan-ro, Jongro-Gu, Seoul, 110-746, Republic of Korea
| | | | | | | |
Collapse
|
|
31
|
Ryoo JH, Park SK, Jung JY. Elevated fasting insulin level significantly increases the risk of microalbuminuria. Circ J 2014; 79:210-5. [PMID: 25391257 DOI: 10.1253/circj.cj-14-0689] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
BACKGROUND Microalbuminuria is significantly associated with long-term prognosis in the general population as well as in diabetic patients. It is well known that insulin resistance (IR) can induce microalbuminuria, but an elevated fasting insulin level, which is an early clinical manifestation of IR, as a risk factor for microalbuminuria has not been clarified, so we investigated the association between fasting insulin level and the development of microalbuminuria in a general population. METHODS AND RESULTS A total of 1,192 non-diabetic Korean men without microalbuminuria in 2005 were followed until 2010. They were categorized into 3 groups according to their fasting insulin levels and monitored for the development of microalbuminuria. The incidence of microalbuminuria was compared among groups, and Cox proportional hazards models were used to calculate the hazard ratios for microalbuminuria according to the fasting insulin levels. During 4,013.0 person-years of follow-up, 51 incident cases of microalbuminuria developed between 2006 and 2010. The incidence of microalbuminuria increased in proportion to the fasting insulin levels (tertile 1: 1.8%, tertile 2: 4.5%, tertile 3: 6.5%, P<0.001). Hazard ratios for microalbuminuria also increased in proportion to the fasting insulin levels [tertile 1: reference, tertile 2: 2.44 (1.01-5.89), tertile 3: 3.30 (1.40-7.78), respectively, P for trend 0.013]. CONCLUSIONS Elevated fasting insulin level was associated with the future development of microalbuminuria.
Collapse
Affiliation(s)
- Jae-Hong Ryoo
- Department of Preventive Medicine, School of Medicine, Kyung Hee University
| | | | | |
Collapse
|
|
32
|
Bjornstad P, Maahs DM, Cherney DZ, Cree-Green M, West A, Pyle L, Nadeau KJ. Insulin sensitivity is an important determinant of renal health in adolescents with type 2 diabetes. Diabetes Care 2014; 37:3033-9. [PMID: 25071077 PMCID: PMC4207204 DOI: 10.2337/dc14-1331] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
OBJECTIVE Diabetic nephropathy (DN) remains the most common cause of end-stage renal disease and is a major cause of mortality in type 2 diabetes. Insulin sensitivity is an important determinant of renal health in adults with type 2 diabetes, but limited data exist in adolescents. We hypothesized that measured insulin sensitivity (glucose infusion rate [GIR]) would be associated with early markers of DN reflected by estimated glomerular filtration rate (eGFR) and albumin-creatinine ratio (ACR) in adolescents with type 2 diabetes. RESEARCH DESIGN AND METHODS Type 2 diabetic (n = 46), obese (n = 29), and lean (n = 19) adolescents (15.1 ± 2.2 years) had GIR measured by hyperinsulinemic-euglycemic clamps. ACR was measured and GFR was estimated by the Bouvet equation (combined creatinine and cystatin C). RESULTS Adolescents with type 2 diabetes had significantly lower GIR, and higher eGFR and ACR than obese or lean adolescents. Moreover, 34% of type 2 diabetic adolescents had albuminuria (ACR ≥30 mg/g), and 24% had hyperfiltration (≥135 mL/min/1.73 m2). Stratifying ACR and eGFR into tertiles, adolescents with type 2 diabetes in the highest tertiles of ACR and eGFR had respectively lower GIR than those in the mid and low tertiles, after adjusting for age, sex, Tanner stage, BMI, and HbA1c (P = 0.02 and P = 0.04). GIR, but not HbA1c, LDL, or systolic blood pressure, was also associated with eGFR after adjusting for sex and Tanner stage (β ± SE: -2.23 ± 0.87; P = 0.02). CONCLUSIONS A significant proportion of adolescents with type 2 diabetes showed evidence of early DN, and insulin sensitivity, rather than HbA1c, blood pressure, or lipid control, was the strongest determinant of renal health.
Collapse
Affiliation(s)
- Petter Bjornstad
- Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO
| | - David M Maahs
- Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO Barbara Davis Center for Diabetes, University of Colorado School of Medicine, Aurora, CO
| | - David Z Cherney
- Division of Nephrology, Department of Medicine, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada
| | - Melanie Cree-Green
- Division of Pediatric Endocrinology, Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO
| | - Amy West
- Division of Pediatric Endocrinology, Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO
| | - Laura Pyle
- Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO
| | - Kristen J Nadeau
- Division of Pediatric Endocrinology, Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO
| |
Collapse
|
|
33
|
Seo JY, Kim MK, Choi BY, Kim YM, Cho SI, Shin J. Elevated brachial-ankle pulse wave velocity is independently associated with microalbuminuria in a rural population. J Korean Med Sci 2014; 29:941-9. [PMID: 25045226 PMCID: PMC4101782 DOI: 10.3346/jkms.2014.29.7.941] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2013] [Accepted: 04/22/2014] [Indexed: 11/27/2022] Open
Abstract
Microalbuminuria is a marker of generalized endothelial dysfunction resulting from arterial stiffness or insulin resistance, and brachial-ankle pulse wave velocity (baPWV) is a good measure of arterial stiffness. We aimed to investigate whether elevated baPWV is independently associated with microalbuminuria. This study included 1,648 individuals aged over 40 who participated in the baseline Multi-Rural Cohort Study conducted in Korean rural communities between 2005 and 2006. Participants were classified into less than 30 mg/g as normoalbuminuria or 30-300 mg/g as microalbuminuriausing urinary albumin creatinine ratio (UACR). The median and Q1-Q3 baPWV values were significantly higher in the microalbuminuric group both in men (1,538, 1,370-1,777 cm/s vs. 1,776, 1,552-2,027 cm/s, P < 0.001) and women (1,461, 1,271-1,687 cm/s vs. 1,645, 1,473-1,915 cm/s, P < 0.001). BaPWV was independently associated with microalbuminuria in both genders after adjusting for pulse rate; fasting blood glucose; triglyceride; homeostatic model assessment insulin resistance (HOMAIR) and, history of hypertension and diabetes. Fasting blood sugar and HOMAIR were judged as having nothing to do with multicolinearity (r = 0.532, P < 0.001). Elevated baPWV was independently associated with microalbuminuria regardless of insulin resistance among rural subjects over 40 yr.
Collapse
Affiliation(s)
- Joo Youn Seo
- Department of Family Medicine, Hanyang University College of Medicine, Seoul, Korea
| | - Mi Kyung Kim
- Department of Preventive Medicine/Institute of Community Health, Hanyang University College of Medicine, Seoul, Korea
| | - Bo Youl Choi
- Department of Preventive Medicine/Institute of Community Health, Hanyang University College of Medicine, Seoul, Korea
| | - Yu-Mi Kim
- Department of Preventive Medicine, Dong-A University College of Medicine, Busan, Korea
| | - Sung-il Cho
- Graduate School of Public Health, Seoul National University, Seoul, Korea
| | - Jinho Shin
- Division of Cardiology, Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea
| |
Collapse
|
|
34
|
Pilz S, Rutters F, Nijpels G, Stehouwer CDA, Højlund K, Nolan JJ, Balkau B, Dekker JM. Insulin sensitivity and albuminuria: the RISC study. Diabetes Care 2014; 37:1597-603. [PMID: 24623021 DOI: 10.2337/dc13-2573] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
OBJECTIVE Accumulating evidence suggests an association between insulin sensitivity and albuminuria, which, even in the normal range, is a risk factor for cardiovascular diseases. We evaluated whether insulin sensitivity is associated with albuminuria in healthy subjects. RESEARCH DESIGN AND METHODS We investigated 1,415 healthy, nondiabetic participants (mean age 43.9 ± 8.3 years; 54.3% women) from the RISC (Relationship between Insulin Sensitivity and Cardiovascular Disease) study, of whom 852 participated in a follow-up examination after 3 years. At baseline, insulin sensitivity was assessed by hyperinsulinemic-euglycemic clamps, expressed as the M/I value. Oral glucose tolerance test-based insulin sensitivity (OGIS), homeostasis model assessment of insulin resistance (HOMA-IR), and urinary albumin-to-creatinine ratio (UACR) were determined at baseline and follow-up. RESULTS Microalbuminuria (UACR ≥30 mg/g) was present in fewer than 2% at either study visit. After multivariate adjustments, there was no cross-sectional association between UACR and any measure of insulin sensitivity. Neither OGIS nor HOMA-IR was significantly associated with follow-up UACR, but in a multivariate regression analysis, baseline M/I emerged as an independent predictor of UACR at follow-up (β-coefficient -0.14; P = 0.001). CONCLUSIONS In healthy middle-aged adults, reduced insulin sensitivity, assessed by hyperinsulinemic-euglycemic clamp, is continuously associated with a greater risk of increasing albuminuria. This finding suggests that reduced insulin sensitivity either is simply related to or might causally contribute to the initial pathogenesis of albuminuria.
Collapse
Affiliation(s)
- Stefan Pilz
- Department of Epidemiology and Biostatistics, EMGO Institute for Health and Care Research, VU University Medical Centre, Amsterdam, the NetherlandsDepartment of Internal Medicine, Division of Endocrinology and Metabolism, Medical University of Graz, Graz, Austria
| | - Femke Rutters
- Department of Epidemiology and Biostatistics, EMGO Institute for Health and Care Research, VU University Medical Centre, Amsterdam, the Netherlands
| | - Giel Nijpels
- Department of General Practice, EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, the Netherlands
| | - Coen D A Stehouwer
- Department of Internal Medicine and Cardiovascular Research Institute, Maastricht University Medical Centre, Maastricht, the Netherlands
| | - Kurt Højlund
- Department of Endocrinology, Odense University Hospital, Odense, Denmark
| | | | - Beverley Balkau
- INSERM, CESP Centre for Research in Epidemiology and Population Health, Epidemiology of Diabetes, Obesity and Chronic Kidney Disease over the Lifecourse and Determinants of Early Nutrition, Villejuif, FranceUniversity of Paris-Sud 11, Villejuif, France
| | - Jacqueline M Dekker
- Department of Epidemiology and Biostatistics, EMGO Institute for Health and Care Research, VU University Medical Centre, Amsterdam, the Netherlands
| | | |
Collapse
|
|
35
|
Zhou Y, Ye L, Wang T, Hong J, Bi Y, Zhang J, Xu B, Sun J, Huang X, Xu M. Free triiodothyronine concentrations are inversely associated with microalbuminuria. Int J Endocrinol 2014; 2014:959781. [PMID: 25484900 PMCID: PMC4248482 DOI: 10.1155/2014/959781] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2014] [Revised: 10/27/2014] [Accepted: 10/28/2014] [Indexed: 01/03/2023] Open
Abstract
Thyroid function and microalbuminuria are both associated with vascular disease and endothelial damage. However, whether thyroid function is associated with microalbuminuria is not well established. The objective was to explore the relationship between thyroid hormones and microalbuminuria in Chinese population. A community-based cross-sectional study was performed among 3,346 Chinese adults (aged ≥ 40 years). Serum free triiodothyronine (FT3), free thyroxine (FT4), and TSH (thyroid stimulating hormone) were determined by chemiluminescent microparticle immunoassay. A single-void first morning urine sample was obtained for urinary albumin-creatinine ratio measurement. The prevalence of microalbuminuria decreased according to FT3 quartiles (13.2, 9.5, 8.6, and 8.2%, P for trend = 0.0005). A fully adjusted logistic regression analysis showed that high FT3 levels were associated with low prevalent microalbuminuria. The adjusted odds ratios for microalbuminuria were 0.61 (95% CI, 0.43-0.87, P = 0.007) when comparing the highest with the lowest quartile of FT3. The exclusion of participants with abnormal FT3 did not appreciably change the results (OR = 0.69, 95% CI, 0.49-0.98, P = 0.02). We concluded that serum FT3 levels, even within the normal range, were inversely associated with microalbuminuria in middle-aged and elderly Chinese adults. FT3 concentrations might play a role in the pathogenesis of microalbuminuria.
Collapse
Affiliation(s)
- Yulin Zhou
- Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrinology and Metabolism, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, 197 Rui-Jin 2nd Road, Shanghai 200025, China
| | - Lei Ye
- Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrinology and Metabolism, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, 197 Rui-Jin 2nd Road, Shanghai 200025, China
- Key Laboratory for Endocrine and Metabolic Diseases of Ministry of Health, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, E-Institute of Shanghai Universities, Shanghai 200025, China
| | - Tiange Wang
- Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrinology and Metabolism, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, 197 Rui-Jin 2nd Road, Shanghai 200025, China
- Key Laboratory for Endocrine and Metabolic Diseases of Ministry of Health, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, E-Institute of Shanghai Universities, Shanghai 200025, China
| | - Jie Hong
- Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrinology and Metabolism, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, 197 Rui-Jin 2nd Road, Shanghai 200025, China
| | - Yufang Bi
- Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrinology and Metabolism, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, 197 Rui-Jin 2nd Road, Shanghai 200025, China
- Key Laboratory for Endocrine and Metabolic Diseases of Ministry of Health, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, E-Institute of Shanghai Universities, Shanghai 200025, China
| | - Jie Zhang
- Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrinology and Metabolism, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, 197 Rui-Jin 2nd Road, Shanghai 200025, China
- Key Laboratory for Endocrine and Metabolic Diseases of Ministry of Health, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, E-Institute of Shanghai Universities, Shanghai 200025, China
| | - Baihui Xu
- Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrinology and Metabolism, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, 197 Rui-Jin 2nd Road, Shanghai 200025, China
- Key Laboratory for Endocrine and Metabolic Diseases of Ministry of Health, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, E-Institute of Shanghai Universities, Shanghai 200025, China
| | - Jichao Sun
- Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrinology and Metabolism, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, 197 Rui-Jin 2nd Road, Shanghai 200025, China
- Key Laboratory for Endocrine and Metabolic Diseases of Ministry of Health, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, E-Institute of Shanghai Universities, Shanghai 200025, China
| | - Xiaolin Huang
- Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrinology and Metabolism, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, 197 Rui-Jin 2nd Road, Shanghai 200025, China
- Key Laboratory for Endocrine and Metabolic Diseases of Ministry of Health, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, E-Institute of Shanghai Universities, Shanghai 200025, China
| | - Min Xu
- Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrinology and Metabolism, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, 197 Rui-Jin 2nd Road, Shanghai 200025, China
- Key Laboratory for Endocrine and Metabolic Diseases of Ministry of Health, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, E-Institute of Shanghai Universities, Shanghai 200025, China
- *Min Xu:
| |
Collapse
|
|
36
|
Factors affecting levels of urinary albumin excretion in the general population of Spain: the Di@bet.es study. Clin Sci (Lond) 2013; 124:269-77. [PMID: 22970892 DOI: 10.1042/cs20120261] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
The present study was undertaken to examine the prevalence of urinary ACR (albumin/creatinine ratio) >30 mg/g and the associated clinical and environmental factors in a representative sample of the population of Spain. Di@bet.es study is a national, cross-sectional population-based survey conducted in 2009-2010. Clinical, metabolic, socio-demographic, anthropometric data and information about lifestyle habit were collected. Those subjects without KDM (known diabetes mellitus) were given an OGTT (oral glucose tolerance test). Albumin and creatinine were measured in a urinary sample and ACR was calculated. The population prevalence of ACR >30 mg/g was 7.65% (adjusted for sex and age). The prevalence of ACR >30 mg/g increased with age (P<0.001). Subjects with carbohydrate metabolism disorders had a greater prevalence of ACR >30 mg/g but after being adjusted for age, sex and hypertension, was significant only in those subjects with UKDM (unknown diabetes mellitus) {OR (odd ratio), 2.07 [95% CI (confidence interval), 1.38-3.09]; P<0.001] and KDM [OR, 3.55 (95% CI, 2.63-4.80); P<0.001]. Prevalence of ACR >30 mg/g was associated with hypertension [OR, 1.48 (95% CI, 1.12-1.95); P=0.001], HOMA-IR (homoeostasis model assessment of insulin resistance) [OR, 1.47 (95% CI, 1.13-1.92); P≤0.01], metabolic syndrome [OR, 2.17 (95% CI, 1.72-2.72); P<0.001], smoking [OR, 1.40 (95% CI, 1.06-1.83); P≤0.05], physical activity [OR, 0.68 (95% CI, 0.54-0.88); P≤0.01] and consumption of fish [OR, 0.38 (95% CI, 0.18-0.78); P≤0.01]. This is the first study that reports the prevalence of ACR >30 mg/g in the Spanish population. The association between clinical variables and other potentially modifiable environmental variables contribute jointly, and sometimes interactively, to the explanation of prevalence of ACR >30 mg/g. Many of these risk factors are susceptible to intervention.
Collapse
|
|
37
|
Chung GE, Heo NJ, Park MJ, Chung SJ, Kang HY, Kang SJ. Helicobacter pylori seropositivity in diabetic patients is associated with microalbuminuria. World J Gastroenterol 2013; 19:97-102. [PMID: 23326169 PMCID: PMC3545230 DOI: 10.3748/wjg.v19.i1.97] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2012] [Revised: 09/17/2012] [Accepted: 09/22/2012] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the relationship between Helicobacter pylori (H. pylori) seropositivity and the presence of microalbuminuria.
METHODS: Between December 2003 and February 2010, asymptomatic individuals who visited the Seoul National University Healthcare System Gangnam Center for a routine check-up and underwent tests for H. pylori immunoglobulin G antibodies and urinary albumin to creatinine ratio (UACR) were included. All study subjects completed a structured questionnaire, anthropometric measurements and laboratory tests. Anti-H. pylori immunoglobulin G was identified using an enzyme-linked immunosorbent assay kit. A random single-void urine sample, collected using a clean-catch technique, was obtained to determine the UACR. The presence of microalbuminuria was defined as a UACR from 30 to 300 μg/mg. The presence of diabetes mellitus (DM) was defined as either a fasting serum glucose level greater than or equal to 126 mg/dL or taking anti-diabetic medication. Multiple logistic regression analysis was performed to identify the risk factors. The dependent variable was microalbuminuria, and the independent variables were the other study variables.
RESULTS: A total of 2716 subjects (male, 71.8%; mean age, 54.9 years) were included. Among them, 224 subjects (8.2%) had microalbuminuria and 324 subjects (11.9%) had been diagnosed with DM. Subjects with microalbuminuria had a significantly higher H. pylori seropositivity rate than subjects without microalbuminuria (60.7% vs 52.8%, P = 0.024). Multivariate analysis after adjustment for age, body mass index (BMI), waist circumference, and glucose and triglyceride levels showed that H. pylori seropositivity was significantly associated with microalbuminuria [odds ratio (OR), 1.40, 95% CI, 1.05-1.89, P = 0.024]. After the data were stratified into cohorts by glucose levels (≤ 100 mg/dL, 100 mg/dL < glucose < 126 mg/dL, and ≥ 126 mg/dL or history of DM), H. pylori seropositivity was found to be significantly associated with microalbuminuria in diabetic subjects after adjusting for age, BMI and serum creatinine level (OR, 2.21, 95% CI, 1.20-4.08, P = 0.011). In addition, the subjects were divided into five groups. Those without microalbuminuria (an UACR of < 30 μg/mg) were divided into four groups in accordance with their UACR values, and subjects with microalbuminuria comprised their own group. Notably, H. pylori seropositivity gradually increased with an increase in UACR (P = 0.001) and was highest in subjects with microalbuminuria (OR, 2.41, 95% CI, 1.14-5.11). This suggests that H. pylori seropositivity is positively associated with microalbuminuria in diabetic subjects.
CONCLUSION: H. pylori seropositivity was independently associated with microalbuminuria, and the prevalence of H. pylori seropositivity was associated with the severity of UACR in diabetic subjects.
Collapse
|
|
38
|
De Cosmo S, Menzaghi C, Prudente S, Trischitta V. Role of insulin resistance in kidney dysfunction: insights into the mechanism and epidemiological evidence. Nephrol Dial Transplant 2012; 28:29-36. [PMID: 23048172 DOI: 10.1093/ndt/gfs290] [Citation(s) in RCA: 146] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Several lines of evidence suggest a pathogenic role of insulin resistance on kidney dysfunction. Potential mechanisms are mostly due to the effect of single abnormalities related to insulin resistance and clustering into the metabolic syndrome. Hyperinsulinemia, which is inevitably associated to insulin resistance in non diabetic states, also appears to play a role on kidney function by inducing glomerular hyperfiltration and increased vascular permeability. More recently, adipocytokine which are linked to insulin resistance, low grade inflammation, endothelial dysfunction and vascular damage have been proposed as additional molecules able to modulate kidney function. In addition, recent evidences point also to a role of insulin resistance at the level of the podocyte, an important player in early phases of diabetic kidney damage, thus suggesting a new mechanism through which a reduction of insulin action can affect kidney function. In fact, mouse models not expressing the podocyte insulin receptor develop podocytes apoptosis, effacement of its foot processes along with thickening of the glomerular basement membrane, increased glomerulosclerosis and albuminuria. A great number of epidemiological studies have repeatedly reported the association between insulin resistance and kidney dysfunction in both non diabetic and diabetic subjects. Among these, studies addressing the impact of insulin resistance genes on kidney dysfunction have played the important role to help establish a cause-effect relationship between these two traits. Finally, numerous independent intervention studies have shown that a favourable modulation of insulin resistance has a positive effect also on urinary albumin and total protein excretion. In conclusion, several data of different nature consistently support the role of insulin resistance and related abnormalities on kidney dysfunction. Intervention trials designed to investigate whether treating insulin resistance ameliorates also hard renal end-points are both timely and needed.
Collapse
Affiliation(s)
- S De Cosmo
- Unit of Endocrinology, IRCSS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
| | | | | | | |
Collapse
|
|
39
|
Nakhjavani M, Morteza A, Jenab Y, Ghaneei A, Esteghamati A, Karimi M, Farokhian A. Gender difference in albuminuria and ischemic heart disease in type 2 diabetes. Clin Med Res 2012; 10:51-6. [PMID: 22031479 PMCID: PMC3355738 DOI: 10.3121/cmr.2011.1021] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
OBJECTIVE The value of urinary albumin excretion in the prediction of myocardial ischemia in men and women with type 2 diabetes is not well understood. We questioned whether gender influences the albuminuria-ischemic heart disease relationship in patients with type 2 diabetes. METHODS We designed a matched case-control study of 926 patients with albuminuria (cases) and 926 age and body mass index matched patients without albuminuria (controls). Ischemic heart disease was defined as the presence of (1) history of angina pectoris or angina equivalent symptoms and critical care unit admission, (2) myocardial infarction and/or electrocardiographic evidence of Q-wave myocardial infarction, (3) coronary revascularization and/or stenting, (4) positive myocardial single-photon emission computed tomography scan, (5) ischemic ST-segment or T-wave changes, and (6) positive stress testing. RESULTS Patients with albuminuria had a lower glomerular filtration rate and a longer diabetes duration than patients without albuminuria. In the group of cases, there were a greater number of men with ischemic heart disease (120 of 370; 32.4%) compared to women (97 of 559; 17.4%) (P<0.001). The odds ratio of having ischemic heart disease according to the presence or absence of albuminuria was 1.25 [95% CI: 1.01-1.56] (P<0.05) in all studied populations, 0.79 [95% CI: 0.51-1.21] (P=0.14) in women, and 2.84 [95% CI: 1.68-4.79] (P<0.001) in men. We showed that diabetes duration, high-density lipoprotein, low-density lipoprotein, and hemoglobin A(1c) influence albuminuria in women, while diabetes duration, fasting blood sugar, and diastolic blood pressure influence albuminuria in men. CONCLUSIONS Men with albuminuria are at increased risk of ischemic heart disease compared to women. This may be related to the role of high-density lipoprotein on the albuminuria-gender relationship.
Collapse
Affiliation(s)
- Manouchehr Nakhjavani
- Endocrinology and Metabolism Research Center-EMRC, Vali-Asr Hospital, Tehran University of Medical Sciences, PO Box 13145-784, Tehran, Iran.
| | | | | | | | | | | | | |
Collapse
|
|
40
|
Haimoto H, Sasakabe T, Umegaki H, Wakai K. Reduction in urinary albumin excretion with a moderate low-carbohydrate diet in patients with type 2 diabetes: a 12-month intervention. Diabetes Metab Syndr Obes 2012; 5:283-91. [PMID: 22924004 PMCID: PMC3422909 DOI: 10.2147/dmso.s34306] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/23/2023] Open
Abstract
INTRODUCTION Urinary albumin excretion (UAE) is a marker of the early phase of diabetic nephropathy. Although a low-carbohydrate diet (LCD) has been shown to effectively improve glycemic control in patients with type 2 diabetes (T2DM), its effects on UAE remain unknown. PATIENTS AND METHODS A total of 124 patients (mean age ± standard deviation, 61.6 ± 9.2 years) with T2DM were instructed to consume a moderate LCD (1734 ± 416 kcal/d; % carbohydrate:fat:protein = 38:37:19) for 12 months. We measured the levels of UAE, hemoglobin A(1c), fasting plasma glucose, fasting serum insulin (IRI), and the serum lipid profiles in the patients and recorded their dosages of antidiabetic drugs during this 12-month period. RESULTS Of the 124 patients, 68 were normoalbuminuric, 50 were microalbuminuric, and six were macroalbuminuric at baseline. The patients had relatively good compliance with the moderate LCD diet. After 12 months, the mean levels of hemoglobin A(1c), fasting plasma glucose, IRI, homeostasis model assessment-estimated insulin resistance, and the body mass index of all participants significantly decreased (P = 0.003 for IRI and P < 0.001 for the other parameters). Among the microalbuminuric patients (n = 50), remission to normoalbuminuria was frequently achieved (52%) and the geometric mean UAE significantly decreased by 53% (95% confidence interval: 43, 62) over 12 months (P < 0.001). After patients taking an angiotensin 2 receptor blocker were excluded, the UAE significantly decreased by 41% (n = 26, 95% confidence interval: 25, 54; P < 0.001). Moreover, the reduction in UAE was significantly and positively correlated with a reduction in homeostasis model assessment-estimated insulin resistance levels (r(s) = 0.308; P = 0.031). CONCLUSION A moderate LCD (38% carbohydrate diet) achieved a remarkable reduction in UAE over 12 months in microalbuminuric patients with T2DM.
Collapse
Affiliation(s)
- Hajime Haimoto
- Department of Internal Medicine, Haimoto Clinic, Kasugai
- Correspondence: Hajime Haimoto, Haimoto Clinic, 1-80 Yayoi, Kasugai, Aichi 486-0838, Japan, Tel +81 568 858 226, Fax +81 568 858 315, Email
| | - Tae Sasakabe
- Department of Clinical Nutrition, Haimoto Clinic, Kasugai
| | - Hiroyuki Umegaki
- Department of Geriatrics, Nagoya University Graduate School of Medicine, Nagoya
| | - Kenji Wakai
- Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan
| |
Collapse
|
|
41
|
Thomas G, Sehgal AR, Kashyap SR, Srinivas TR, Kirwan JP, Navaneethan SD. Metabolic syndrome and kidney disease: a systematic review and meta-analysis. Clin J Am Soc Nephrol 2011; 6:2364-73. [PMID: 21852664 PMCID: PMC3186450 DOI: 10.2215/cjn.02180311] [Citation(s) in RCA: 422] [Impact Index Per Article: 30.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2011] [Accepted: 06/15/2011] [Indexed: 12/22/2022]
Abstract
BACKGROUND AND OBJECTIVES Observational studies have reported an association between metabolic syndrome (MetS) and microalbuminuria or proteinuria and chronic kidney disease (CKD) with varying risk estimates. We aimed to systematically review the association between MetS, its components, and development of microalbuminuria or proteinuria and CKD. DESIGN, SETTING, PARTICIPANTS AND MEASUREMENTS AND POPULATION: We searched MEDLINE (1966 to October 2010), SCOPUS, and the Web of Science for prospective cohort confidence interval (CI) studies that reported the development of microalbuminuria or proteinuria and/or CKD in participants with MetS. Risk estimates for eGFR <60 ml/min per 1.73 m(2) were extracted from individual studies and pooled using a random effects model. The results for proteinuria outcomes were not pooled because of the small number of studies. RESULTS Eleven studies (n = 30,146) were included. MetS was significantly associated with the development of eGFR <60 ml/min per 1.73 m(2) (odds ratio, 1.55; 95% CI, 1.34, 1.80). The strength of this association seemed to increase as the number of components of MetS increased (trend P value = 0.02). In patients with MetS, the odds ratios (95% CI) for development of eGFR <60 ml/min per 1.73 m(2) for individual components of MetS were: elevated blood pressure 1.61 (1.29, 2.01), elevated triglycerides 1.27 (1.11, 1.46), low HDL cholesterol 1.23 (1.12, 1.36), abdominal obesity 1.19 (1.05, 1.34), and impaired fasting glucose 1.14 (1.03, 1.26). Three studies reported an increased risk for development of microalbuminuria or overt proteinuria with MetS. CONCLUSIONS MetS and its components are associated with the development of eGFR <60 ml/min per 1.73 m(2) and microalbuminuria or overt proteinuria.
Collapse
Affiliation(s)
- George Thomas
- Department of Nephrology and Hypertension, Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, Ohio
| | - Ashwini R. Sehgal
- Division of Nephrology, MetroHealth Medical Center, Case Western Reserve University, Cleveland, Ohio
| | - Sangeeta R. Kashyap
- Department of Endocrinology, Endocrinology and Metabolism Institute, Cleveland Clinic, Cleveland, Ohio; and
| | - Titte R. Srinivas
- Department of Nephrology and Hypertension, Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, Ohio
| | - John P. Kirwan
- Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio
| | - Sankar D. Navaneethan
- Department of Nephrology and Hypertension, Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, Ohio
| |
Collapse
|
|
42
|
Glucose intolerance in renal transplant recipients is associated with increased urinary albumin excretion. Transpl Immunol 2011; 24:241-5. [DOI: 10.1016/j.trim.2011.02.001] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2010] [Revised: 02/17/2011] [Accepted: 02/17/2011] [Indexed: 11/20/2022]
|
|
43
|
De Cosmo S, Prudente S, Lamacchia O, Lapice E, Morini E, Di Paola R, Copetti M, Ruggenenti P, Remuzzi G, Vaccaro O, Cignarelli M, Trischitta V. PPARγ2 P12A polymorphism and albuminuria in patients with type 2 diabetes: a meta-analysis of case-control studies. Nephrol Dial Transplant 2011; 26:4011-6. [PMID: 21493814 DOI: 10.1093/ndt/gfr187] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Insulin resistance has a role in diabetic nephropathy. The A12 variant of the PPARγ2 P121A polymorphism has been firmly associated with reduced risk of insulin resistance, while its role on the risk of albuminuria in patients with type 2 diabetes is uncertain. This study investigated whether the PPARγ2 P12A polymorphism modulates the risk of albuminuria in these patients. METHODS We tested the association between the A12 variant and albuminuria in three new case-control studies in diabetic patients from Italy (n = 841, n = 623 and n = 714 patients, respectively) and then performed a meta-analysis of all studies available to date. The nine studies we meta-analysed (six previously published and three presented here) comprised a total of 2376 cases and 4188 controls. RESULTS In none of the three new studies was a significant association observed with odds ratio (OR) [95% confidence intervals (95% CI)] being 1.115, 0.799 and 0.849 (P = 0.603, 0.358 and 0.518, respectively). At meta-analysis, the overall OR (95% CI) for association between A12 and albuminuria was 0.694 (0.528-0.912). A significant heterogeneity of the genetic effect was observed (P = 0.026), which was totally explained by the different method of urine collection and albuminuria definition utilized across the studies. In fact, most of the effect was observed in the four studies determining albumin excretion rate rather than in those using albumin concentration in a single spot (OR, 95% CI: 0.529, 0.397-0.706, P = 0.0000164 and 0.919, 0.733-1.153, P = 0.47, respectively). CONCLUSION The present study shows that the PPARγ2 Ala12 variant is significantly associated with a reduced risk of albuminuria among patients with type 2 diabetes.
Collapse
Affiliation(s)
- Salvatore De Cosmo
- Department of Cardiovascular, Endocrine and Metabolic Diseases, IRCCS Casa Sollievo della Sofferenza,San Giovanni Rotondo, Italy.
| | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
44
|
Hsu CC, Chang HY, Huang MC, Hwang SJ, Yang YC, Tai TY, Yang HJ, Chang CT, Chang CJ, Li YS, Shin SJ, Kuo KN. Association between insulin resistance and development of microalbuminuria in type 2 diabetes: a prospective cohort study. Diabetes Care 2011; 34:982-7. [PMID: 21335369 PMCID: PMC3064061 DOI: 10.2337/dc10-1718] [Citation(s) in RCA: 66] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
OBJECTIVE An association between insulin resistance and microalbuminuria in type 2 diabetes has often been found in cross-sectional studies. We aimed to reassess this relationship in a prospective Taiwanese cohort of type 2 diabetic subjects. RESEARCH DESIGN AND METHODS We enrolled 738 normoalbuminuric type 2 diabetic subjects, aged 56.6 ± 9.0 years, between 2003 and 2005 and followed them through the end of 2009. Average follow-up time was 5.2 ± 0.8 years. We used urine albumin-to-creatinine ratio to define microalbuminuria and the homeostasis model assessment of insulin resistance (HOMA-IR) to assess insulin resistance. The incidence rate ratio and Cox proportional hazards model were used to evaluate the association between HOMA-IR and development of microalbuminuria. RESULTS We found incidences of microalbuminuria of 64.8, 83.5, 93.3, and 99.0 per 1,000 person-years for the lowest to highest quartiles of HOMA-IR. Compared with those in the lowest quartile of HOMA-IR, the incidence rate ratios for those in the 2nd, 3rd, and highest quartiles were 1.28 (95% CI 0.88-1.87), 1.44 (0.99-2.08), and 1.52 (1.06-2.20), respectively (trend test: P < 0.001). By comparison with those in the lowest quartile, the adjusted hazard ratios were 1.37 (0.93-2.02), 1.66 (1.12-2.47), and 1.76 (1.20-2.59) for those in the 2nd, 3rd, and highest HOMA-IR quartiles, respectively. CONCLUSIONS According to the dose-response effects of HOMA-IR shown in this prospective study, we conclude that insulin resistance could significantly predict development of microalbuminuria in type 2 diabetic patients.
Collapse
Affiliation(s)
- Chih-Cheng Hsu
- Division of Health Policy Research and Development, Institute of Population Health Sciences, National Health Research Institutes, Taiwan
| | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
45
|
Hu W, Feng P. Elevated serum chemerin concentrations are associated with renal dysfunction in type 2 diabetic patients. Diabetes Res Clin Pract 2011; 91:159-63. [PMID: 21144611 DOI: 10.1016/j.diabres.2010.11.016] [Citation(s) in RCA: 57] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2010] [Revised: 11/10/2010] [Accepted: 11/15/2010] [Indexed: 11/19/2022]
Abstract
AIM Chemerin, a new adipocytokine, has been suggested to be linked to obesity-induced insulin resistance and type 2 diabetes. The association of plasma chemerin levels with diabetic nephropathy, however, is unknown. Therefore, this study aims to determine whether plasma chemerin levels are associated with renal function in type 2 diabetic patients. METHODS A total of 116 type 2 diabetic patients and 38 healthy subjects were enrolled in this study. Serum levels of chemerin were measured by enzyme-linked immunosorbent assay. RESULTS Serum chemerin was significantly elevated in type 2 diabetic patients with macroalbuminuria compared with control subjects and diabetic patients with normoalbuminuria and microalbuminuria. No differences were found in the level of serum chemerin between diabetic patients with normoalbuminuria and microalbuminuria and control subjects. Serum chemerin was positively correlated with age, body mass index (BMI), systolic blood pressure (SBP), C-reactive protein (CRP), blood urea nitrogen (BUN), serum creatinine and serum triglycerides, and negatively correlated with creatinine clearance Stepwise regression analysis showed that creatinine clearance and serum creatinine remained significantly associated with serum chemerin. CONCLUSION Serum chemerin levels are strongly associated with renal function in diabetic patients.
Collapse
Affiliation(s)
- Wenchao Hu
- Department of Endocrinology, General Hospital of Tianjin Medical University, 154 Anshan Street, Heping District, 300052, Tianjin, PR China
| | | |
Collapse
|
|
46
|
Abstract
Microalbuminuria is considered a marker of heightened risk for cardiovascular events. We examined cardiovascular risk factors, including inflammatory cytokines, which contribute to urinary albumin excretion (UAE) in a cross-sectional study of African Americans aged 18-49 years. Measurements included a timed overnight urine collection for UAE, blood pressure (BP), body mass index, glucose, lipids, insulin and inflammatory cytokines. Non-normally distributed variables were log transformed for analysis using multiple linear regressions. Data were obtained from 488 participants with mean age 37.8 years; 50% were obese, 42% had hypertension. Log UAE correlated significantly with systolic BP (SBP) (geometric mean ratio=1.011; 95% confidence interval 1.003-1.019). When subjects were stratified into four UAE groups, the only variables significantly different between groups were SBP (P=0.013) and diastolic BP (P=0.036). There were no statistically significant associations with obesity, metabolic parameters, insulin resistance or any inflammatory cytokines identified. In young, relatively healthy, African Americans, BP level is significantly associated with levels of UAE even below the threshold for microalbuminuria. The presence of diabetes and insulin resistance in the absence of high BP did not seem to contribute significantly to UAE in this cohort.
Collapse
|
|
47
|
Prudente S, Morini E, Trischitta V. Insulin signaling regulating genes: effect on T2DM and cardiovascular risk. Nat Rev Endocrinol 2009; 5:682-93. [PMID: 19924153 DOI: 10.1038/nrendo.2009.215] [Citation(s) in RCA: 66] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Type 2 diabetes mellitus (T2DM) is a complex disorder that has a heterogeneous genetic and environmental background. In this Review, we discuss the role of relatively infrequent polymorphisms of genes that regulate insulin signaling (including the K121Q polymorphism of ENPP1, the G972R polymorphism of IRS1 and the Q84R polymorphism of TRIB3) in T2DM and other conditions related to insulin resistance. The biological relevance of these three polymorphisms has been very thoroughly characterized both in vitro and in vivo and the available data indicate that they all affect insulin signaling and action as well as insulin secretion. They also affect insulin-mediated regulation of endothelial cell function. In addition, several reports indicate that the effects of all three polymorphisms on the risk of T2DM and cardiovascular diseases related to insulin resistance depend on the clinical features of the individual, including their body weight and age at disease onset. Thus, these polymorphisms might be used to demonstrate how difficult it is to ascertain the contribution of relatively infrequent genetic variants with heterogeneous effects on disease susceptibility. Unraveling the role of such variants might be facilitated by improving disease definition and focusing on specific subsets of patients.
Collapse
Affiliation(s)
- Sabrina Prudente
- IRCCS Casa Sollievo della Sofferenza, Mendel Institute, Rome, Italy
| | | | | |
Collapse
|
|
48
|
De Cosmo S, Motterlini N, Prudente S, Pellegrini F, Trevisan R, Bossi A, Remuzzi G, Trischitta V, Ruggenenti P, on behalf of the BENEDICT Study Group. Impact of the PPAR-gamma2 Pro12Ala polymorphism and ACE inhibitor therapy on new-onset microalbuminuria in type 2 diabetes: evidence from BENEDICT. Diabetes 2009; 58:2920-9. [PMID: 19720797 PMCID: PMC2780880 DOI: 10.2337/db09-0407] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
OBJECTIVE Cross-sectional studies found less microalbuminuria in type 2 diabetic patients with the Ala12 allele of the peroxisome proliferator-activated receptor-gamma2 (PPAR-gamma2) Pro12Ala polymorphism. We prospectively evaluated the association between Pro12Ala polymorphism (rs1801282) and new-onset microalbuminuria. RESEARCH DESIGN AND METHODS Pro12Ala polymorphism was genotyped by TaqMan-based assay in genomic DNA of 1,119 consenting patients from BErgamo NEphrologic DIabetic Complications Trial (BENEDICT)-a prospective, randomized trial evaluating ACE inhibition effect on new-onset microalbuminuria (albuminuria 20-200 microg/min in at least two of three consecutive overnight urine collections in two consecutive visits) in hypertensive type 2 diabetes with albuminuria <20 microg/min at inclusion. RESULTS Baseline characteristics of Ala (Ala/Ala or Ala/Pro) carriers and Pro/Pro homozygotes were similar, with a nonsignificant trend to lower albuminuria (P = 0.1107) in the 177 Ala carriers. Over a median (interquartile range) of 44.0 (17.1-51.9) months, 7 (4%) Ala carriers and 86 (9.1%) Pro/Pro homozygotes developed microalbuminuria (hazard ratio [HR] 0.45 [95% CI 0.21-0.97]; P = 0.042). Final albuminuria was significantly lower in Ala carriers than Pro/Pro homozygotes (7.3 +/- 9.1 vs. 10.5 +/- 24.9 microg/min, respectively), even after adjustment for baseline albuminuria (P = 0.048). Baseline and follow-up blood pressure and metabolic control were similar in both groups. Incidence of microalbuminuria was significantly decreased by ACE versus non-ACE inhibitor therapy in Pro/Pro homozygotes (6.3 vs. 11.9%, respectively, HR 0.46 [0.29-0.72]; P < 0.001). CONCLUSIONS In type 2 diabetes, the Ala allele protects from worsening albuminuria and new-onset microalbuminuria, and ACE inhibition blunts the excess risk of microalbuminuria associated with the Pro/Pro genotype. Evaluating Pro12Ala polymorphism may help identifying patients at risk who may benefit the most from early renoprotective therapy.
Collapse
Affiliation(s)
- Salvatore De Cosmo
- Unit of Endocrinology, IRCCS “Casa Sollievo della Sofferenza,” San Giovanni Rotondo, Italy
| | - Nicola Motterlini
- Clinical Research Center for Rare Diseases “Aldo & Cele Daccò,” Mario Negri Institute for Pharmacological Research, Bergamo, Italy
| | - Sabrina Prudente
- Research Unit of Diabetes and Endocrine Diseases, IRCCS “Casa Sollievo della Sofferenza,” San Giovanni Rotondo, Italy
- IRCCS “Casa Sollievo della Sofferenza,” Mendel Institute, Rome, Italy
| | - Fabio Pellegrini
- Unit of Biostatistics, IRCCS “Casa Sollievo della Sofferenza,” San Giovanni Rotondo, Italy
| | - Roberto Trevisan
- Unit of Diabetology, Azienda Ospedaliera Ospedali Riuniti di Bergamo, Bergamo, Italy
| | - Antonio Bossi
- Unit of Diabetology, Treviglio Hospital, Treviglio, Italy
| | - Giuseppe Remuzzi
- Clinical Research Center for Rare Diseases “Aldo & Cele Daccò,” Mario Negri Institute for Pharmacological Research, Bergamo, Italy
- Unit of Nephrology, Azienda Ospedaliera Ospedali Riuniti di Bergamo, Bergamo, Italy
- Corresponding author: Giuseppe Remuzzi,
| | - Vincenzo Trischitta
- Research Unit of Diabetes and Endocrine Diseases, IRCCS “Casa Sollievo della Sofferenza,” San Giovanni Rotondo, Italy
- IRCCS “Casa Sollievo della Sofferenza,” Mendel Institute, Rome, Italy
- Department of Medical Pathophysiology, “Sapienza” University, Rome, Italy
| | - Piero Ruggenenti
- Clinical Research Center for Rare Diseases “Aldo & Cele Daccò,” Mario Negri Institute for Pharmacological Research, Bergamo, Italy
- Unit of Nephrology, Azienda Ospedaliera Ospedali Riuniti di Bergamo, Bergamo, Italy
| | | |
Collapse
|
|
49
|
Li XY, Xu M, Wang JG, Wang XJ, Huang Y, Cheng Q, Huang HE, Li R, Xiang J, Tan JR, Dai M, Ning G. Serum C-reactive protein (CRP) and microalbuminuria in relation to fasting and 2-h postload plasma glucose in a Chinese population. Clin Endocrinol (Oxf) 2009; 70:691-7. [PMID: 18691271 DOI: 10.1111/j.1365-2265.2008.03371.x] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
OBJECTIVE Serum C-reactive protein (CRP) and microalbuminuria are predictors of cardiovascular disease. The association of these factors of cardiovascular risk with fasting and 2-h postload plasma glucose in a group of Chinese subjects was investigated. DESIGN This was a cross-sectional cohort study. SUBJECTS AND METHODS In 1776 subjects randomly selected from the permanent residents of a community in the city of Shanghai, China, a simplified 75-g oral glucose tolerance test (fasting and 2-h postload blood sampling only) was performed, and serum CRP concentrations and urinary albumin : creatinine ratio were measured. RESULTS Serum CRP concentration significantly increased from 1.62 mg/l in normoglycaemic subjects to 2.63 mg/l in subjects with impaired glucose regulation, and to 3.09 mg/l in newly diagnosed diabetic patients (P < 0.0001). The corresponding prevalence of microalbuminuria also increased from 4.3% to 6.6% and to 11.4% (P < 0.0001). Both before and after adjustment for confounders, fasting and 2-h postload plasma glucose levels were significantly associated with serum CRP concentration and the risk of microalbuminuria (P < 0.003). However, the association for CRP tended to be more prominent with 2-h postload plasma glucose than with fasting plasma glucose. Indeed, with adjustments applied, for 1 SD change in fasting and 2-h postload plasma glucose concentration, serum CRP concentration increased by 14% and 18% (between the two regression coefficients, P = 0.01), respectively. With similar adjustments, for 1 SD change in fasting and 2-h postload plasma glucose concentration, the odds of microalbuminuria increased by 28% and 32% (P = 0.28 for the difference between 28% and 32%), respectively. CONCLUSIONS Our finding suggests that in Chinese plasma glucose, especially 2-h postload, is associated with biological markers of cardiovascular disease, such as serum CRP concentration and microalbuminuria.
Collapse
Affiliation(s)
- Xiao-Ying Li
- Shanghai Clinical Center for Endocrine and Metabolic Diseases, Division of Endocrinology and Metabolism, E-Institutes of Shanghai Universities, Shanghai, China
| | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
50
|
Esteghamati A, Ashraf H, Nakhjavani M, Najafian B, Hamidi S, Abbasi M. Insulin resistance is an independent correlate of increased urine albumin excretion: a cross-sectional study in Iranian Type 2 diabetic patients. Diabet Med 2009; 26:177-81. [PMID: 19236623 DOI: 10.1111/j.1464-5491.2008.02653.x] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
AIMS To assess the association of insulin resistance with increased urinary albumin excretion (UAE) in a cohort of Iranian Type 2 diabetic patients. METHODS Three hundred and sixty-one men and 472 women with Type 2 diabetes were enrolled from three different outpatient clinics (Tehran, Iran) during the period 2005-2008. Patients with obstructive uropathy, severe heart failure, liver disease, cancer, autoimmune disease and macroalbuminuria were not included. Microalbuminuria (MA; defined as UAE >or= 30 mg/day) was found in 242 (29.1%) patients; 591 (70.9%) subjects had normoalbuminuria (UAE < 30 mg/day). Insulin resistance was assessed using homeostasis model assessment of insulin resistance (HOMA-IR). RESULTS HOMA-IR index values were higher in subjects with MA than those with normoalbuminuria (P < 0.00001). Adjusted values (for age, sex and duration of diabetes) of UAE and HOMA-IR were 11.81 +/- 7.51 (mg/day) and 3.30 +/- 2.21 in normoalbuminuric and 75.36 +/- 55.57 (mg/day) and 4.98 +/- 3.22 in the MA group, respectively (P < 0.00001 for all). Multiple regression analysis showed that UAE was predicted by HOMA-IR, independently of age, duration of diagnosed diabetes, triglycerides, waist circumference, metabolic control, blood pressure and related treatments (P < 0.00001). When patients were categorized into quartiles of HOMA-IR, those of the fourth quartile (i.e. the most insulin resistant) were at a higher risk of increased UAE than other quartiles [odds ratio (OR) 3.7 (95% confidence intervals 2.7-6.2)]. CONCLUSIONS In Iranian Type 2 diabetic patients, albuminuria was strongly associated with insulin resistance. HOMA-IR is an independent predictor of UAE.
Collapse
Affiliation(s)
- A Esteghamati
- Department of Endocrinology, Endocrinology and Metabolism Research Center, Vali-asr Hospital, Tehran University of Medical Sciences/University of Tehran, Tehran, Iran.
| | | | | | | | | | | |
Collapse
|