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Circulating ceramide levels are dysregulated in kidney disease. However, their associations with rapid decline in kidney function (RDKF) and end-stage kidney disease (ESKD) in patients with type 2 diabetes (T2D) are unknown. In this prospective study of 1746 T2D participants, we examined the association of plasma ceramide Cer16:0, Cer18:0, Cer24:0, and Cer24:1 with RDKF, defined as an estimated glomerular filtration rate (eGFR) decline of 5 ml/min/1.73 m2 per year or greater, and ESKD defined as eGFR <15/min/1.73 m2 for at least 3 months, on dialysis or renal death at follow-up. During a median follow-up period of 7.7 years, 197 patients experienced RDKF. Ceramide Cer24:0 (odds ratio [OR] = 0.71, 95% CI 0.56-0.90) and ratios Cer16:0/Cer24:0 (OR = 3.54 [1.70-7.35]), Cer18:0/Cer24:0 (OR = 1.89 [1.10-3.25]), and Cer24:1/Cer24:0 (OR = 4.01 [1.93-8.31]) significantly associated with RDKF in multivariable analysis; 124 patients developed ESKD. The ratios Cer16:0/Cer24:0 (hazard ratio [HR] = 3.10 [1.44-6.64]) and Cer24:1/Cer24:0 (HR = 4.66 [1.93-11.24]) significantly associated with a higher risk of ESKD. The Cer24:1/Cer24:0 ratio improved risk discrimination for ESKD beyond traditional risk factors by small but statistically significant margin (Harrell C-index difference: 0.01; P = 0.022). A high ceramide risk score also associated with RDKF (OR = 2.28 [1.26-4.13]) compared to lower risk score. In conclusion, specific ceramide levels and their ratios are associated with RDKF and conferred an increased risk of ESKD, independently of traditional risk factors, including baseline renal functions in patients with T2D.
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Ceramidas , Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Ceramidas/sangre , Masculino , Femenino , Persona de Mediana Edad , Anciano , Tasa de Filtración Glomerular , Estudios Prospectivos , Riñón/fisiopatología , Fallo Renal Crónico/sangreRESUMEN
BACKGROUND: Angiogenin, an enzyme belonging to the ribonucleases A superfamily, plays an important role in vascular biology. Here, we sought to study the association of plasma angiogenin and major adverse cardiovascular events (MACEs) in patients with type 2 diabetes (T2D). METHODS: This prospective study included 1083 T2D individuals recruited from a secondary hospital and a primary care facility. The primary outcome was a composite of four-point MACE (nonfatal myocardial infarction, stroke, unstable angina pectoris leading to hospitalization and cardiovascular death). Circulating angiogenin was measured by a proximity extension assay. Cox regression models were used to evaluate the association of baseline plasma angiogenin with the risk of MACE. RESULTS: During a median follow-up of 9.3 years, 109 (10%) MACE were identified. Plasma angiogenin was significantly higher in participants with MACE than in those without MACE (P < 0.001). Doubling of plasma angiogenin concentration was associated with a 3.10-fold (95% CI 1.84-5.22) increased risk for MACE. The association was only moderately attenuated after adjustment for demographic and cardiometabolic risk factors (adjusted HR 2.38, 95% CI 1.34-4.23) and remained statistically significant after additional adjustment for estimated glomerular filtration rate (eGFR) and urinary albumin to creatinine ratio (uACR) (adjusted HR 1.90, 95% CI 1.02-3.53). A consistent outcome was obtained when plasma angiogenin was analysed as a categorical variable in tertiles. CONCLUSIONS: Plasma angiogenin was associated with the risk of future cardiovascular events in patients with T2D and may be a promising novel biomarker for identifying high-risk T2D patients for early management.
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Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 2 , Humanos , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/complicaciones , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/diagnóstico , Infarto del Miocardio/complicaciones , Estudios Prospectivos , Ribonucleasa Pancreática , Factores de RiesgoRESUMEN
Macroscopic loss of extracellular matrix can lead to chronic defects in skin wound healing, but supplementation of extracellular matrix holds promise for facilitating wound closure, particularly in diabetic wound healing. We recently showed that the extracellular matrix proteoglycan agrin accelerates cutaneous wound healing by improving mechanoperception of migrating keratinocytes and allowing them to respond to mechanical stresses through matrix metalloproteinase 12 (MMP12). RNA-sequencing analysis revealed that in addition to a disorganized extracellular matrix, agrin-depleted skin cells have impaired YAP/TAZ transcriptional outcomes, leading us to hypothesize that YAP/TAZ, as central mechanosensors, drive the functionality of agrin-MMP12 signaling during cutaneous wound repair. In this study, we demonstrate that agrin activates YAP/TAZ during migration of keratinocytes after wounding in vitro and in vivo. Mechanistically, YAP/TAZ sustain agrin and MMP12 protein expression during migration after wounding through positive feedback. YAP/TAZ silencing abolishes agrin-MMP12-mediated force recognition and geometrical constraints. Importantly, soluble agrin therapy accelerates wound closure in diabetic mouse models by engaging MMP12-YAP. Because patients with diabetic foot ulcers and impaired wound healing have reduced expression of agrin-MMP12 that correlates with YAP/TAZ inactivation, we propose that timely activation of YAP/TAZ by soluble agrin therapy can accentuate mechanobiological microenvironments for efficient wound healing, under normal and diabetic conditions.
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AIM: Skeletal muscle mass to visceral fat area ratio (SVR) has been recognised as an index of sarcopenic obesity. SVR is associated with type 2 diabetes mellitus (T2DM), metabolic syndrome and arterial stiffness which are known risk factors for cognitive dysfunction. We aimed to investigate association between SVR and cognitive function in patients with T2DM. METHODS: This was a cross-sectional study of 1326 patients with T2DM and mean age 61.3 ± 8.0 years. SVR was assessed based on bioelectrical impedance measurements of muscle mass and visceral fat area (VFA). Cognitive function was assessed using Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Linear regression was used to examine the association between SVR in quartiles and RBANS score, adjusting for demographics, education, presence of depressive symptoms, clinical covariates and medications. RESULTS: The lower SVR quartiles were negatively associated with RBANS total score in the unadjusted analysis. The corresponding coefficients for Quartiles 1 and 2 SVR were -3.79 (95 % CI -5.39 to -2.19; p < 0.001) and -1.47 (95 % CI -2.86 to -0.07; p = 0.039) in fully adjusted analysis. The negative association between Quartile 1 SVR and RBANS score was evident in immediate memory, delayed memory, visuo-spatial construction, language and attention domains. Muscle mass and VFA alone had weaker associations with RBANS scores. CONCLUSION: Our study demonstrated, for the first time, an independent association between reduced SVR and lower cognitive function. This is evident in global and multiple cognitive domains. The synergistic effects of reduced muscle mass and visceral obesity may be more pronounced than their independent effects on cognitive function.
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Disfunción Cognitiva , Diabetes Mellitus Tipo 2 , Humanos , Persona de Mediana Edad , Anciano , Diabetes Mellitus Tipo 2/diagnóstico , Grasa Intraabdominal , Estudios Transversales , Cognición , Disfunción Cognitiva/complicaciones , Disfunción Cognitiva/epidemiología , Músculo EsqueléticoRESUMEN
Introduction: In 2022, the Minister for Health of Singapore launched Healthier SG, a national strategy in championing the shift towards a population health approach. Method: The Singapore Heart Foundation conducted a series of roundtable discussions, also attended by representatives of the Singapore Cardiac Society and the Chapter of Cardiologists of the Academy of Medicine Singapore. During the meetings, the authors formulated interventions supportive of Healthier SG that specifically aimed to uplift the state of cardiovascular (CV) preventive care in Singapore. Results: In line with Healthier SG, the authors propose a 3-pronged approach ("Healthier Heart SG") to augment the success of Healthier SG in achieving good CV outcomes. This proposal includes the following components: (1) a call to update the standards of care in addressing the 5 main modifiable risk factors of cardiovascular disease (CVD); (2) patient education through cooperation between healthcare professionals and community partners for a whole-of-system approach; and (3) support for integrated care, including access to cardiac rehabilitation in the community, improved referral processes and access to nutrition/dietetics counselling and tobacco cessation, optimal use of information technology, and continued CV research. Conclusion: Healthier Heart SG would bring the standards of care and CV care delivery in Singapore closer to achieving the vision of proactive prevention of CVD and CV morbidity and mortality. This can only be achieved through the concerted efforts of healthcare professionals, policymakers and community partners, coupled with the cooperation of community members.
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Enfermedades Cardiovasculares , Sociedades Médicas , Singapur/epidemiología , Humanos , Enfermedades Cardiovasculares/prevención & control , Cardiología/organización & administración , Educación del Paciente como Asunto , Rehabilitación Cardiaca/métodos , Fundaciones/organización & administración , Factores de Riesgo de Enfermedad CardiacaRESUMEN
CONTEXT: Patients with younger onset of type 2 diabetes (YT2D) have increased risk for kidney failure compared to those with late onset. However, the mechanism of diabetic kidney disease (DKD) progression in this high-risk group is poorly understood. OBJECTIVES: To identify novel biomarkers and potential causal proteins associated with DKD progression in patients with YT2D. DESIGN AND PARTICIPANTS: Among YT2D (T2D onset age ≤ 40 years), 144 DKD progressors (cases) were matched for T2D onset age, sex, and ethnicity with 292 non-progressors (controls) and divided into discovery and validation sets. DKD progression was defined as decline of estimated glomerular filtration rate (eGFR) of 3ml/min/1.73m2 or greater or 40% decline in eGFR from baseline. 1472 plasma proteins were measured through a multiplex immunoassay that uses a proximity extension assay technology. Multivariable logistic regression was used to identify proteins associated with DKD progression. Mendelian randomization (MR) was used to evaluate causal relationship between plasma proteins and DKD progression. RESULTS: 42 plasma proteins were associated with DKD progression, independent of traditional cardio-renal risk factors, baseline eGFR and urine albumin-to-creatinine ratio (uACR). The proteins identified were related to inflammatory and remodelling biological processes. Our findings suggested angiogenin as one of the top signals (odds ratio =5.29, 95% CI 2.39-11.73, P = 4.03 × 10-5). Furthermore, genetically determined plasma angiogenin level was associated with increased odds of DKD progression. CONCLUSION: Large-scale proteomic analysis identified novel proteomic biomarkers for DKD progression in YT2D. Genetic evidence suggest a causal role of plasma angiogenin in DKD progression.
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AIM: Among multi-ethnic Asians, type 2 diabetes (T2D) clustered in three subtypes; mild obesity-related diabetes (MOD), mild age-related diabetes with insulin insufficiency (MARD-II) and severe insulin-resistant diabetes with relative insulin insufficiency (SIRD-RII) had differential cardio-renal complication risk. We assessed the proteomic profiles to identify subtype specific biomarkers and its association with diabetes complications. METHODS: 1448 plasma proteins at baseline were measured and compared across the T2D subtypes. Multivariable cox regression was used to assess associations between significant proteomics features and cardio-renal complications. RESULTS: Among 645 T2D participants (SIRD-RII [19%], MOD [45%], MARD-II [36%]), 295 proteins expression differed significantly across the groups. These proteins were enriched in cell adhesion, neurogenesis and inflammatory response processes. In SIRD-RII group, ADH4, ACY1, THOP1, IGFBP2, NEFL, ENTPD2, CALB1, HAO1, CTSV, ITGAV, SCLY, EDA2R, ERBB2 proteins significantly associated with progressive CKD and LILRA5 protein with incident heart failure (HF). In MOD group, TAFA5, RSPO3, EDA2R proteins significantly associated with incident HF. In MARD-II group, FABP4 protein significantly associated with progressive CKD and PTPRN2 protein with major adverse cardiovascular events. Genetically determined NEFL and CALB1 were associated with kidney function decline. CONCLUSIONS: Each T2D subtype has unique proteomics signature and association with clinical outcomes and underlying mechanisms.
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Pueblo Asiatico , Diabetes Mellitus Tipo 2 , Proteómica , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/sangre , Masculino , Femenino , Persona de Mediana Edad , Anciano , Biomarcadores/sangre , Nefropatías Diabéticas/epidemiología , Nefropatías Diabéticas/sangre , Nefropatías Diabéticas/etiologíaRESUMEN
AIMS: We aim to determine the association of seven major candidate protein biomarkers and diabetic kidney disease (DKD) progression among Asians with young-onset type 2 diabetes mellitus (T2DM). METHODS: 824 T2DM patients (onset ≤ 40 years old) were classified as DKD progressors based on yearly estimated glomerular filtration rate (eGFR) decline of >3 ml/min/1.73 m2 or >40 % from baseline. Plasma leucine-rich α-2-glycoprotein 1 (pLRG1), tumor necrosis factor-receptor 1 (pTNF-R1), pigment epithelium-derived factor (pPEDF), urinary α-1-microglobulin (uA1M), kidney injury molecular 1 (uKIM-1), haptoglobin (uHP) and uromodulin (uUMOD) were measured using enzyme-linked immunoassays. RESULTS: Over 5.7 years of follow-up, 25.2 % of patients were DKD progressors. Elevated levels of pLRG1, pTNF-R1, pPEDF, uA1M, uKIM-1 and uHP were associated with DKD progression. The association between pTNF-R1 levels and DKD progression persisted after adjusting for clinical covariates (OR 1.84, 95 %CI 1.44-2.34, p < 0.001). The effects of pTNF-R1 were partially mediated through hyperglycemia (8 %) and albuminuria (10 %). Inclusion of pTNF-R1 in a clinical variable-based model improved the area under the receiver operating characteristics curve for predicting DKD progression by 0.02, from 0.72 (95 %CI 0.68-0.76) to 0.74 (95 %CI 0.70-0.78), p = 0.099. CONCLUSIONS: Among seven major candidate proteins, pTNF-R1, partially mediated through hyperglycemia and albuminuria, robustly predicted DKD progression among Asians with young-onset T2DM.
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CONTEXT: Leucine-rich α-2-glycoprotein 1 (LRG1) has been implicated in the pathogenesis of diabetic complications, but its association with cognitive function remains unclear. OBJECTIVE: Our primary objective is to investigate the longitudinal association between LRG1 and cognitive function in patients with type 2 diabetes mellitus (T2DM). Secondarily, we determine the causal relationship using Mendelian randomization (MR) and the role of arterial stiffness as a potential mediator. METHODS: T2DM patients (n = 1039; age = 64.1 ± 6.4 years) were followed-up for 5.3 ± 1.2 years. Plasma LRG1 was measured at baseline using enzyme-linked immunosorbent assay. Baseline and follow-up cognitive function was assessed using Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). One-sample MR was performed with rs4806985 as plasma LRG1-associated single-nucleotide polymorphism. Mediation analysis was performed to examine if pulse wave velocity (PWV), an arterial stiffness index, mediated the association between plasma LRG1 and follow-up cognitive function. RESULTS: Elevated baseline natural log (Ln)-transformed LRG1 was inversely associated with baseline and follow-up RBANS total score with adjusted coefficients -1.38 (95% CI -2.55 to -.21; P = .021) and -1.38 (95% CI -2.70 to -.07; P = .039), respectively. Genetically predicted higher levels of plasma LRG1 was associated with lower follow-up RBANS total score with coefficient -7.44 (95% CI -14.14 to -.74; P = .030) per unit increase in LnLRG1. Higher PWV accounted for 27.7% of the association between LnLRG1 and follow-up RBANS total score. CONCLUSION: Baseline plasma LRG1 was associated with lower cognitive function at follow-up in patients with T2DM, mediated by PWV. MR analysis provided evidence of an association between genetically influenced plasma LRG1 and lower cognitive function at follow-up.
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Cognición , Diabetes Mellitus Tipo 2 , Glicoproteínas , Polimorfismo de Nucleótido Simple , Humanos , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/psicología , Diabetes Mellitus Tipo 2/complicaciones , Femenino , Persona de Mediana Edad , Masculino , Anciano , Cognición/fisiología , Glicoproteínas/sangre , Glicoproteínas/genética , Pueblo Asiatico/genética , Disfunción Cognitiva/sangre , Disfunción Cognitiva/genética , Disfunción Cognitiva/etiología , Rigidez Vascular/fisiología , Análisis de la Aleatorización Mendeliana , Estudios de Seguimiento , Análisis de la Onda del Pulso , Estudios LongitudinalesRESUMEN
Background: As numerous studies highlighted the importance of maintaining proper foot care (FC) behaviours among individuals with diabetes to prevent complications, we sought to assess FC behaviours among patients with diabetes and to identify the factors associated with the practice of diabetic FC. Methods: We used a cross-sectional design and collected data through self-reported questionnaires administered to a sample of 586 patients from five medical centres. We conducted descriptive and inferential analyses to explore the relationships between potential risk and protective factors and FC behaviours. Results: Overall, 429 individuals (73.2%) had good FC behaviours, while 157 (26.8%) displayed poor FC behaviours. Furthermore, we identified eight influencing factors on FC behaviours, including smoking status, the availability of a caregiver, the presence of diabetic foot ulcers, amputation history, FC knowledge, subjective norms in diabetes self-care behaviour, diabetes-related stress, and quality of life index values. The logistic regression analysis showed that current smokers were 60% less likely to practice good FC compared to non-smokers (odds ratio (OR) = 0.40; 95%; confidence interval (CI) = 0.22-0.73). Having a caregiver decreased the likelihood of practicing good FC by 50% (OR = 0.52; 95% CI = 0.33-0.84), while having diabetic foot ulcers doubled it (OR = 2.65; 95% CI = 1.26-5.54). Additionally, more FC knowledge increased the likelihood by 20% (OR = 1.21; 95% CI = 1.10-1.33), and higher diabetes-related stress increased it by 1.03 times (OR = 1.03; 95% CI = 1.02-1.05). Conclusions: Our findings underscore the interplay of various factors influencing FC behaviours among individuals with diabetes and call for targeted interventions and tailored strategies to improve FC practices in this vulnerable population.
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Diabetes Mellitus Tipo 2 , Pie Diabético , Humanos , Estudios Transversales , Masculino , Femenino , Pie Diabético/psicología , Persona de Mediana Edad , Diabetes Mellitus Tipo 2/terapia , Diabetes Mellitus Tipo 2/psicología , Anciano , Autocuidado , Encuestas y Cuestionarios , Conductas Relacionadas con la Salud , Adulto , Conocimientos, Actitudes y Práctica en Salud , Factores de RiesgoRESUMEN
Introduction: Phase angle (PhA), derived from bioelectrical impedance analysis (BIA), is the angle of vector determined by the body's resistance and reactance. It indicates cellular integrity and hydration status. Though extracellular volume excess was associated with chronic kidney disease (CKD) progression, the association between PhA and CKD progression is unknown. Matrix metalloproteinase-2 (MMP-2) is a member of zinc-dependent endopeptidase family and promotes renal interstitial fibrosis. We investigated association between PhA and CKD progression, and whether the association was through MMP-2 in patients with type 2 diabetes mellitus (T2DM). Method: We conducted a prospective study on 1,078 patients with T2DM (mean age 58.9±9.1 years). PhA was measured using BIA. CKD progression was defined as ≥25% decrease in estimated glomerular filtration rate (eGFR) from baseline with deterioration across eGFR categories. Multiplex immunoassay was used to quantitate MMP-2. We examined association between PhA and CKD progression using Cox proportional hazards model, adjusting for demographics, clinical parameters and medications. Results: Over 8.6 years of follow-up, 43.7% of participants had CKD progression. Compared to tertile 3 PhA (higher level), tertiles 1 and 2 PhA were associated with higher hazards of CKD progression, with corresponding unadjusted hazard ratios (HRs) of 2.27 (95% confidence interval [CI] 1.80-2.87, P<0.001) and 1.57 (95% CI 1.24-2.01, P<0.001). The positive association between tertiles 1 and 2 PhA with CKD progression persisted in the fully adjusted model with corresponding HRs of 1.71 (95% CI 1.30-2.26, P<0.001) and 1.46 (95% CI 1.13-1.88, P=0.004). MMP-2 accounted for 14.7% of association between tertile 1 PhA and CKD progression. Conclusion: Our findings revealed a previously unobserved association between BIA-derived lower PhA and CKD progression through MMP-2 in patients with T2DM.
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Diabetes Mellitus Tipo 2 , Progresión de la Enfermedad , Impedancia Eléctrica , Tasa de Filtración Glomerular , Metaloproteinasa 2 de la Matriz , Insuficiencia Renal Crónica , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/fisiopatología , Persona de Mediana Edad , Insuficiencia Renal Crónica/fisiopatología , Estudios Prospectivos , Masculino , Femenino , Metaloproteinasa 2 de la Matriz/metabolismo , Anciano , Nefropatías Diabéticas/fisiopatología , Nefropatías Diabéticas/etiología , Nefropatías Diabéticas/epidemiología , Modelos de Riesgos ProporcionalesRESUMEN
INTRODUCTION@#The risk for diabetes progression varies greatly in individuals with type 2 diabetes mellitus (T2DM). We aimed to study the clinical determinants of diabetes progression in multiethnic Asians with T2DM.@*MATERIALS AND METHODS@#A total of 2057 outpatients with T2DM from a secondary-level Singapore hospital were recruited for the study. Diabetes progression was defined as transition from non-insulin use to requiring sustained insulin treatment or glycated haemoglobin (HbA1c) ≥8.5% when treated with 2 or more oral hypoglycaemic medications. Multivariable logistic regression (LR) was used to study the clinical and biochemical variables that were independently associated with diabetes progression. Forward LR was then used to select variables for a parsimonious model.@*RESULTS@#A total of 940 participants with no insulin use or indication for insulin treatment were analysed. In 3.2 ± 0.4 (mean ± SD) years' follow-up, 163 (17%) participants experienced diabetes progression. Multivariable LR revealed that age at T2DM diagnosis (odds ratio [95% confidence interval], 0.96 [0.94-0.98]), Malay ethnicity (1.94 [1.19-3.19]), baseline HbA1c (2.22 [1.80-2.72]), body mass index (0.96 [0.92-1.00]) and number of oral glucose-lowering medications (1.87 [1.39-2.51]) were independently associated with diabetes progression. Area under receiver operating characteristic curve of the parsimonious model selected by forward LR (age at T2DM diagnosis, Malay ethnicity, HbA1c and number of glucose-lowering medication) was 0.76 (95% CI, 0.72-0.80).@*CONCLUSION@#Young age at T2DM diagnosis, high baseline HbA1c and Malay ethnicity are independent determinants of diabetes progression in Asians with T2DM. Further mechanistic studies are needed to elucidate the pathophysiology underpinning progressive loss of glycaemic control in patients with T2DM.
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<p><b>INTRODUCTION</b>Diabetes mellitus (DM) is a major cause of chronic kidney disease (CKD). The epidemiology of CKD secondary to type 2 DM (T2DM) (i.e. diabetic nephropathy (DN)) has not been well studied in Singapore, a multi-ethnic Asian population. We aimed to determine the prevalence of CKD in adult patients with T2DM.</p><p><b>MATERIALS AND METHODS</b>We conducted a cross-sectional study on patients (n = 1861) aged 21 to 89 years with T2DM who had attended the DM centre of a single acute care public hospital or a primary care polyclinic between August 2011 and November 2013. Demographic and clinical data were obtained from patients using a standard questionnaire. Spot urine and fasting blood samples were sent to an accredited hospital laboratory for urinary albumin, serum creatinine, HbA1c and lipid measurement. CKD was defined and classified using the 2012 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines and classification.</p><p><b>RESULTS</b>The distribution by risk of adverse CKD outcomes was: low risk, 47%; moderate risk, 27.2%; high risk, 12.8%; and very high risk, 13%. The prevalence of CKD in patients with T2DM was 53%. Variables significantly associated with CKD include neuropathy, blood pressure ≥140/80 mmHg, triglycerides ≥1.7 mmol, body mass index, duration of diabetes, HbA1c ≥8%, age, cardiovascular disease, and proliferative retinopathy.</p><p><b>CONCLUSION</b>CKD was highly prevalent among patients with T2DM in Singapore. Several risk factors for CKD are well recognised and amenable to intervention. Routine rigorous screening for DN and enhanced programme for global risk factors reduction will be critical to stem the tide of DN.</p>
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Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Transversales , Diabetes Mellitus Tipo 2 , Modelos Logísticos , Prevalencia , Insuficiencia Renal Crónica , Diagnóstico , Epidemiología , Factores de Riesgo , SingapurRESUMEN
Statins are commonly used in the treatment of hyperlipidaemia. Although the benefits of statins are well-documented, they have the potential to cause myopathy and rhabdomyolysis due to the complex interactions of drugs, comorbidities and genetics. The cytochrome P450 family consists of major enzymes involved in drug metabolism and bioactivation. This article aims to highlight drug interactions involving statins, as well as provide updated recommendations and approaches regarding the safe and appropriate use of statins in the primary care setting.
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Anciano , Femenino , Humanos , Claritromicina , Colchicina , Creatina Quinasa , Metabolismo , Citocromo P-450 CYP3A , Metabolismo , Interacciones Farmacológicas , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Lovastatina , Debilidad Muscular , Músculos , Mialgia , Seguridad del PacienteRESUMEN
Cardiovascular disease due to atherosclerosis is a leading cause of death around the world, including Singapore. Current treatment strategies primarily target low-density lipoprotein (LDL) cholesterol levels. Low levels of high-density lipoprotein (HDL) cholesterol and high triglyceride (TG) levels have been shown to increase the risk of coronary heart disease, but the clinical benefits of raising low HDL cholesterol have only been proven in a limited number of studies. This guide provides an approach on managing low HDL cholesterol levels in terms of lifestyle modifications and pharmacotherapy.
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Humanos , Masculino , Persona de Mediana Edad , Enfermedad Coronaria , Quimioterapia Combinada , Ejercicio Físico , Fenofibrato , Hipertrigliceridemia , Quimioterapia , Terapéutica , Hipoalfalipoproteinemias , Quimioterapia , Terapéutica , Hipolipemiantes , Estilo de Vida , SimvastatinaRESUMEN
@#<p><strong>OBJECTIVES:</strong> An inter-arm difference in systolic blood pressure (IADSBP) of 10 mmHg or more has been associated with cardiovascular disease (CVD) and increased mortality in T2DM patients. We aim to study ethnic disparity in IADSBP and its determinants in a multi-ethnic T2DM Asian cohort.<br /><strong>METHODOLOGY:</strong> Bilateral blood pressures were collected sequentially in Chinese (n=654), Malays (n=266) and Indians (n=313). IADSBP was analyzed as categories (<br /><strong>RESULTS:</strong> Malays (27.4%) and Indians (22.4%) had higher prevalence of IADSBP ?10 mmHg than Chinese (17.4%) (p=0.002). After adjustment for age, gender, duration of diabetes, hemoglobin A1c, body mass index (BMI), heart rate, pulse wave velocity (PWV), estimated glomerular filtration rate (eGFR), albumin-to-creatinine ratio (ACR), smoking, hypertension, soluble receptor for advanced glycation end products (sRAGE), and usage of hypertension medications, ethnicity remained associated with IADSBP. While Malays were more likely to have IADSBP ?10 mmHg than Chinese (OR=1.648, 95%CI: 1.138-2.400, p=0.009), Indians had comparable odds with the Chinese. BMI (OR=1.054, 95%CI: 1.022-1.087, p=0.001) and hypertension (OR=2.529, 95%CI: 1.811-3.533, p<0.001) were also associated with IADSBP ?10 mmHg.<br /><strong>CONCLUSION:</strong> IADSBP in Malays were more likely to be ?10 mmHg than the Chinese which may explain their higher risk for CVD and mortality. Measuring bilateral blood pressures may identify high-risk T2DM individuals for intensive risk factor-management.</p>