ABSTRACT
Fluorescence spectroscopy coupled with a random forest machine learning algorithm offers a promising non-invasive approach for diagnosing glycosuria, a condition characterized by excess sugar in the urine of diabetic patients. This study investigated the ability of this method to differentiate between diabetic and healthy control urine samples. Fluorescent spectra were captured from urine samples using a Xenon arc lamp emitting light within the 200 to 950 nm wavelength range, with consistent fluorescence emission observed at 450 nm under an excitation wavelength of 370 nm. Healthy control samples were also analyzed within the same spectral range for comparison. To distinguish spectral differences between healthy and infected samples, the random forest (RF) and K-Nearest Neighbors (KNN) machine learning algorithms have been employed. These algorithms automatically recognize spectral patterns associated with diabetes, enabling the prediction of unknown classifications based on established samples. Principal component analysis (PCA) was utilized for dimensionality reduction before feeding the data to RF and KNN for classification. The model's classification performance was evaluated using 10-fold cross-validation, resulting in the proposed RF-based model achieving accuracy of 96 %, specificity of 100 %, sensitivity of 93 %, and precision of 100 %. These results suggest that the proposed method holds promise for a more convenient and potentially more accurate method for diagnosing glycosuria in diabetic patients.
Subject(s)
Algorithms , Glycosuria , Machine Learning , Principal Component Analysis , Spectrometry, Fluorescence , Humans , Spectrometry, Fluorescence/methods , Glycosuria/diagnosis , Glycosuria/urine , Diabetes Mellitus/urine , Diabetes Mellitus/diagnosis , Male , FemaleABSTRACT
Background: More than 700 million people worldwide suffer from diseases of the pancreas, such as diabetes, pancreatitis and pancreatic cancer. Often dysregulation of potassium (K+) channels, co-transporters and pumps can promote development and progression of many types of these diseases. The role of K+ transport system in pancreatic cell homeostasis and disease development remains largely unexplored. Potassium isotope analysis (δ41K), however, might have the potential to detect minute changes in metabolic processes relevant for pancreatic diseases. Methods: We assessed urinary K isotope composition in a case-control study by measuring K concentrations and δ41K in spot urines collected from patients diagnosed with pancreatic cancer (n=18), other pancreas-related diseases (n=14) and compared those data to healthy controls (n=16). Results: Our results show that urinary K+ levels for patients with diseased pancreas (benign and pancreatic cancer) are significantly lower than the healthy controls. For δ41K, the values tend to be higher for individuals with pancreatic cancer (mean δ41K = -0.58 ± 0.33) than for healthy individuals (mean δ41K = -0.78 ± 0.19) but the difference is not significant (p=0.08). For diabetics, urinary K+ levels are significantly lower (p=0.03) and δ41K is significantly higher (p=0.009) than for the healthy controls. These results suggest that urinary K+ levels and K isotopes can help identify K disturbances related to diabetes, an associated factors of all-cause mortality for diabetics. Conclusion: Although the K isotope results should be considered exploratory and hypothesis-generating and future studies should focus on larger sample size and δ41K analysis of other K-disrupting diseases (e.g., chronic kidney disease), our data hold great promise for K isotopes as disease marker.
Subject(s)
Diabetes Mellitus , Pancreatic Neoplasms , Potassium , Humans , Pancreatic Neoplasms/urine , Male , Female , Case-Control Studies , Middle Aged , Aged , Potassium/urine , Diabetes Mellitus/urine , Diabetes Mellitus/metabolism , Adult , Pancreas/metabolism , Isotopes/urineABSTRACT
PURPOSE: New-onset diabetes after transplantation (NODAT) is a frequent metabolic complication associated with podocyte damage and renal allograft dysfunction. Thus, Wilm's tumor-1 (WT-1) protein, as a podocyte marker, holds promise as an option to evaluate renal allograft dysfunction in NODAT. Therefore, the study aimed to investigate urinary WT-1 levels in NODAT patients during the first year after kidney transplantation (KTx). MATERIALS AND METHODS: KTx patients were categorized into non-NODAT and NODAT groups. Fasting blood glucose, glycated hemoglobin (HbA1c), urinary albumin/creatinine ratio (ACR), serum creatinine, estimated glomerular filtration rate (eGFR), and urinary WT-1 were measured at 3, 6, 9, and 12-months post-KTx. RESULTS: The NODAT group manifested elevated levels of blood glucose and HbA1c during the first year post-KTx. Also, exhibited elevations in ACR and serum creatinine levels at 6, 9, and 12-months post-KTx when compared to non-NODAT group. Conversely, eGFR values in the NODAT group demonstrated significant declines at 3, 6, and 9-months post-KTx relative to non-NODAT. Furthermore, NODAT group exhibited a median annual eGFR of 47 âmL/min/1.73 âm2. Urinary WT-1 levels at 3, 6, 9, and 12-months post-KTx were significantly higher in the NODAT group compared to non-NODAT. Additionally, noteworthy positive correlations were identified between urinary WT-1 and HbA1c levels, along with significant negative correlations between urinary WT-1 and eGFR at the 3, 6, 9, and 12-months post-KTx. CONCLUSION: The increased urinary WT-1 levels from 3-months post-KTx in NODAT patients may indicate the first sign of podocyte injury, predicting a renal allograft dysfunction in these patients.
Subject(s)
Diabetes Mellitus , Glomerular Filtration Rate , Kidney Transplantation , WT1 Proteins , Humans , Kidney Transplantation/adverse effects , Male , Female , Middle Aged , Adult , WT1 Proteins/urine , Diabetes Mellitus/urine , Biomarkers/urine , Biomarkers/blood , Allografts , Prognosis , Follow-Up Studies , Glycated Hemoglobin/metabolismABSTRACT
Urinary extracellular vesicles (uEV) are a topical source of non-invasive biomarkers for health and diseases of the urogenital system. However, several challenges have become evident in the standardization of uEV pipelines from collection of urine to biomarker analysis. Here, we studied the effect of pre-analytical variables and developed means of quality control for uEV isolates to be used in transcriptomic biomarker research. We included urine samples from healthy controls and individuals with type 1 or type 2 diabetes and normo-, micro- or macroalbuminuria and isolated uEV by ultracentrifugation. We studied the effect of storage temperature (-20°C vs. -80°C), time (up to 4 years) and storage format (urine or isolated uEV) on quality of uEV by nanoparticle tracking analysis, electron microscopy, Western blotting and qPCR. Urinary EV RNA was compared in terms of quantity, quality, and by mRNA or miRNA sequencing. To study the stability of miRNA levels in samples isolated by different methods, we created and tested a list of miRNAs commonly enriched in uEV isolates. uEV and their transcriptome were preserved in urine or as isolated uEV even after long-term storage at -80°C. However, storage at -20°C degraded particularly the GC-rich part of the transcriptome and EV protein markers. Transcriptome was preserved in RNA samples extracted with and without DNAse, but read distributions still showed some differences in e.g. intergenic and intronic reads. MiRNAs commonly enriched in uEV isolates were stable and concordant between different EV isolation methods. Analysis of never frozen uEV helped to identify surface characteristics of particles by EM. In addition to uEV, qPCR assays demonstrated that uEV isolates commonly contained polyoma viruses. Based on our results, we present recommendations how to store and handle uEV isolates for transcriptomics studies that may help to expedite standardization of the EV biomarker field.
Subject(s)
Biomarkers/urine , Diabetes Mellitus/urine , Extracellular Vesicles/metabolism , Transcriptome/genetics , Adult , Case-Control Studies , Humans , Quality ControlABSTRACT
Importance: The appropriate target of glycemic control in diabetic kidney disease is unclear. Objective: To investigate optimal on-treatment glycemic levels associated with slowing of diabetic kidney disease progression. Design, Setting, and Participants: This retrospective cohort study was conducted using nationwide Korean cohorts from the National Health Information Database from 2005 to 2019. Included individuals were adults with diabetes using antihyperglycemic agents with and without chronic kidney disease (CKD) identified from participants aged 40 to 74 years in a nationwide health screening survey conducted from 2009 to 2010. Data were analyzed from October 2020 through March 2021. Exposure: On-treatment fasting blood glucose (FBG) level. Main Outcomes and Measures: The primary outcome was a composite of doubling of serum creatinine, end-stage kidney disease, or death from CKD. Results: Among 183â¯049 adults with diabetes using antihyperglycemic agents (mean [SD] age, 61.7 [8.4] years; 99â¯110 [54.1%] men), there were 131â¯401 individuals with dipstick albuminuria or an estimated glomerular filtration rate (eGFR) of 15 to 59 mL/min/1.73 m2 (mean [SD] age, 62.4 [8.3] years; 71â¯280 [54.2%] men) and 51â¯648 individuals with no CKD (mean [SD] age, 59.6 [8.4] years; 27â¯830 [53.9%] men). During 9 years of follow-up, the primary outcome occurred among 13â¯802 individuals with CKD (10.5%) and 1421 individuals with no CKD (2.8%). On-treatment FBG level had a J-shaped hazard ratio (HR) curve for the primary outcome. Among patients with albuminuria, FBG levels of 126 mg/dL to less than 140 mg/dL (HR, 0.87; 95% CI, 0.81-0.94) and 140 mg/dL to less than 160 mg/dL (HR, 0.90; 95% CI, 0.84-0.96) were associated with decreased risk and levels of 160 mg/dL to less than 180 mg/dL were associated with increased risk (HR, 1.10; 95% CI, 1.03-1.18) compared with FBG levels of 110 mg/dL to less than 126 mg/dL. Among patients with decreased eGFR, FBG levels of 80 mg/dL to less than 100 mg/dL (HR, 1.30; 95% CI, 1.20-1.42) and levels of 160 mg/dL to less than 180 mg/dL (HR, 1.13; 95% CI, 1.04-1.23) were associated with increased risk of the primary outcome compared with FBG levels of 110 mg/dL to less than 126 mg/dL. Among patients with no CKD, FBG levels of 80 mg/dL to less than 100 mg/dL (HR, 1.29; 95% CI, 1.01-1.65) and levels of 126 mg/dL to less than 140 mg/dL (HR, 1.23; 95% CI, 1.03-1.47) were associated with increased risk compared with FBG levels of 110 mg/dL to less than 126 mg/dL. Among patients with no albuminuria at baseline, FBG levels of 140 mg/dL to less than 160 mg/dL (HR, 1.14; 95% CI, 1.09-1.20) were associated with increased risk of new-onset albuminuria, while levels of 100 mg/dL to less than 110 mg/dL were not associated with increased risk compared with FBG levels of 110 mg/dL to less than 126 mg/dL. For all-cause mortality, while FBG levels of 160 mg/dL to less than 180 mg/dL (HR, 1.20; 95% CI, 1.12-1.28) were associated with increased risk among patients with albuminuria, FBG levels of 140 mg/dL to less than 160 mg/dL were associated with increased risk among patients with decreased eGFR (HR, 1.10; 95% CI, 1.04-1.16) and those with no CKD (HR, 1.10; 95% CI, 1.00-1.21) compared with levels of 110 mg/dL to less than 126 mg/dL. Conclusions and Relevance: These findings suggest that intensive vs standard glucose control may not be associated with increased protection for the progression of established diabetic kidney disease and that timely control is important for prevention. However, careful glycemic control would still be associated with improved overall outcomes among patients with CKD, particularly those with no albuminuria.
Subject(s)
Albuminuria/urine , Blood Glucose/analysis , Creatinine/blood , Diabetic Nephropathies/blood , Diabetic Nephropathies/epidemiology , Adult , Aged , Cardiovascular Diseases/complications , Cardiovascular Diseases/mortality , Cohort Studies , Diabetes Mellitus/blood , Diabetes Mellitus/drug therapy , Diabetes Mellitus/urine , Diabetic Nephropathies/drug therapy , Diabetic Nephropathies/prevention & control , Disease Progression , Female , Humans , Hypoglycemic Agents/therapeutic use , Male , Middle Aged , Republic of Korea/epidemiology , Retrospective StudiesABSTRACT
Background: To compare the efficacy of lipid accumulation product (LAP) and urine glucose excretion (UGE) in predicting diabetes and evaluate whether the combination of LAP and UGE would help to improve the efficacy of using LAP alone or UGE alone in identifying diabetes. Methods: Data from 7485 individuals without prior history of diabetes who participated in a cross-sectional survey in Jiangsu, China, were analyzed. Each participant underwent an oral glucose-tolerance test. Operating characteristic curves (ROC) and logistic regression analyses were used to evaluate the performance of LAP and UGE in identification of newly diagnosed diabetes (NDM) and prediabetes (PDM). Results: For subjects with NDM, the area under the ROC curve was 0.72 for LAP and 0.85 for UGE, whereas for PDM, these values were 0.62 and 0.61, respectively. Furthermore, LAP exhibited a comparable sensitivity with UGE in detecting NDM (76.4% vs 76.2%, p = 0.31). In predicting PDM, LAP showed a higher sensitivity than UGE (66.4% vs 42.8%, p < 0.05). The combination of LAP and UGE demonstrated a significantly higher sensitivity than that of LAP alone and UGE alone for identification of NDM (93.6%) and PDM (80.1%). Moreover, individuals with both high LAP and high UGE had significantly increased risk of NDM and PDM than those with both low LAP and low UGE. Conclusions: The combination of LAP and UGE substantially improved the efficacy of using LAP and using UGE alone in detecting diabetes, and may be a novel approach for mass screening in the general population.
Subject(s)
Diabetes Mellitus/diagnosis , Glycosuria/diagnosis , Lipid Accumulation Product , Adult , Asian People , Diabetes Mellitus/metabolism , Diabetes Mellitus/urine , Female , Glucose/metabolism , Glycosuria/metabolism , Glycosuria/urine , Humans , Male , Mass Screening , Middle AgedABSTRACT
[Figure: see text].
Subject(s)
Albuminuria/diagnosis , Creatinine/urine , Diabetes Mellitus/urine , Hypertension/urine , Adult , Aged , Albuminuria/epidemiology , Glomerular Filtration Rate , Humans , Middle Aged , Renal Insufficiency, Chronic/diagnosisABSTRACT
BACKGROUND: Urinary liver-type fatty acid-binding protein (L-FABP) is a well-known marker of proximal tubular impairment. We evaluated the relationship between cardiovascular disease (CVD) risk factors and levels of L-FABP in a cross-sectional community-based study. Participants with normoalbuminuria and normal estimated glomerular filtration rate (eGFR), that is, non-chronic kidney disease (non-CKD), were enrolled in this study. To the best of our knowledge, this is the first study to focus on the association between CVD risk factors and a proximal tubular marker in the Japanese general population with normoalbuminuria and normal eGFR. METHODS: The present study is part of the Sasayama study. The participants included 1000 community residents (447 men and 553 women) aged 40-64 years without a history of CVD or renal dysfunction. Out of these participants 375 men and 477 women, defined as non-CKD, were included for further analysis. In each sex, the highest quintile group was considered to have high-normal L-FABP levels. A multiple logistic regression model was used to evaluate the relationship between risk factors for CVD and high-normal L-FABP levels in the non-CKD participants. We performed a similar analysis using the high-normal urinary albumin to creatinine ratio (UACR) as a dependent variable instead of L-FABP. RESULTS: Among the non-CKD participants, in the highest quintile group (Q5, top 20%), L-FABP was ≥2.17 µg/gCre in men and ≥ 2.83 µg/gCre in women. In women, the multivariate odds ratio was 3.62 (1.45-9.00) for high-normal L-FABP in the presence of diabetes mellitus (DM) compared with that in the group without DM. However, the relationship between DM and the UACR level was not significant. In men, DM was significantly associated with high-normal UACR. However, the relationship with L-FABP levels was not significant. CONCLUSIONS: The presence of DM was more strongly related to high-normal L-FABP levels than to high-normal UACR in women even at the stage of normoalbuminuria and normal eGFR. Our results were also consistent with the findings of a previous study where women were more prone to nonalbuminuric renal impairment compared to men, although further studies are required to confirm the results.
Subject(s)
Diabetes Mellitus/urine , Fatty Acid-Binding Proteins/urine , Heart Disease Risk Factors , Adult , Albuminuria , Biomarkers/urine , Cohort Studies , Cross-Sectional Studies , Datasets as Topic , Female , Glomerular Filtration Rate , Humans , Japan , Male , Middle Aged , Odds Ratio , Sex FactorsABSTRACT
The factors contributing to increased morbidity and mortality in SARS-CoV-2 infection are diverse, and include diabetes, obesity, Chronic Obstructive Pulmonary Disease (COPD), advanced age, and male sex. Although there is no obvious connection between these, they do have one common denominator-they all have a tendency towards lower urine pH, which may indicate a lower-than-normal tissue pH. Furthermore, it has been shown that lower pH has two important negative influences: 1) it enhances viral fusion via the endosomal route, thereby facilitating viral multiplication; and 2) it facilitates increased production of inflammatory cytokines, thereby exacerbating the cytokine storm. This paper discusses published literature on lower tissue/interstitial pH in those diseases/co-morbidities that are known risk factors of severe COVID-19, and hypothesize that small doses of baking soda could be a simple, cost-effective, and rapid method of reducing both morbidity and mortality in COVID-19 patients.
Subject(s)
Acidosis/metabolism , COVID-19/metabolism , Cytokines/metabolism , Diabetes Mellitus/metabolism , Obesity/metabolism , Pulmonary Disease, Chronic Obstructive/metabolism , Virus Internalization , Acidosis/drug therapy , Acidosis/urine , Age Factors , COVID-19/epidemiology , COVID-19/mortality , COVID-19/physiopathology , Cytokine Release Syndrome , Diabetes Mellitus/epidemiology , Diabetes Mellitus/urine , Early Medical Intervention , Humans , Hydrogen-Ion Concentration , Obesity/epidemiology , Obesity/urine , Pulmonary Disease, Chronic Obstructive/epidemiology , Pulmonary Disease, Chronic Obstructive/urine , Risk Factors , SARS-CoV-2 , Severity of Illness Index , Sex Factors , Sodium Bicarbonate/therapeutic use , Urine/chemistryABSTRACT
Carnosine is a naturally occurring dipeptide (ß-alanine-L-histidine) which supports physiological homeostasis by buffering intracellular pH, chelating metals, and conjugating with and neutralizing toxic aldehydes such as acrolein. However, it is not clear if carnosine can support cardiovascular function or modify cardiovascular disease (CVD) risk. To examine this, we measured urinary levels of nonconjugated carnosine and its acrolein conjugates (carnosine-propanal and carnosine-propanol) in participants of the Louisville Healthy Heart Study and examined associations with indices of CVD risk. We found that nonconjugated carnosine was significantly associated with hypertension (p = 0.011), heart failure (p = 0.015), those categorized with high CVD risk (p < 0.001), body mass index (BMI; p = 0.007), high sensitivity C-reactive protein (hsCRP; p = 0.026), high-density lipoprotein (HDL; p = 0.007) and certain medication uses. Levels of carnosine-propanal and carnosine-propanol demonstrated significant associations with BMI, blood glucose, HDL and diagnosis of diabetes. Carnosine-propanal was also associated with heart failure (p = 0.045) and hyperlipidemia (p = 0.002), but no associations with myocardial infarction or stroke were identified. We found that the positive associations of carnosine conjugates with diabetes and HDL remain statistically significant (p < 0.05) in an adjusted, linear regression model. These findings suggest that urinary levels of nonconjugated carnosine, carnosine-propanal and carnosine-propanol may be informative biomarkers for the assessment of CVD risk-and particularly reflective of skeletal muscle injury and carnosine depletion in diabetes.
Subject(s)
Carnosine/urine , Heart Failure/epidemiology , Hyperlipidemias/epidemiology , Hypertension/epidemiology , Acrolein/metabolism , Adult , Biomarkers/metabolism , Biomarkers/urine , Blood Glucose/analysis , Body Mass Index , C-Reactive Protein/analysis , Carnosine/metabolism , Cohort Studies , Diabetes Mellitus/blood , Diabetes Mellitus/epidemiology , Diabetes Mellitus/urine , Female , Heart Failure/blood , Heart Failure/urine , Humans , Hyperlipidemias/blood , Hyperlipidemias/urine , Hypertension/blood , Hypertension/urine , Linear Models , Lipoproteins, HDL/blood , Male , Risk Assessment/methods , Risk FactorsABSTRACT
AIMS: To evaluate diagnostic performance of glomerular filtration rate (GFR) estimated by modification of diet in renal disease (MDRD), chronic kidney disease epidemiology collaboration (CKD-EPI), full age spectrum (FAS), and revised Lund-Malmö (r-LM) equations in adults with diabetes. METHODS: Individuals were included in this cross-sectional study if they had at least 1 measurement of technetium-99m diethylenetriamine-pentaacetic acid (99mTc-DTPA) GFR (mGFR) and serum creatinine (1487 patients with 2703 measures). GFR calculated by estimation equations was compared with mGFR. Diagnostic performance was assessed using concordance correlation coefficient (CCC), bias, precision, accuracy, reduced major axis regression (RMAR), and Bland-Altman plot. Analysis was repeated in subgroups based on sex, diabetes type, Hemoglobin A1C, and GFR level. RESULTS: Of all patients, 1189 (86%) had type 2 diabetes. Mean mGFR, MDRD, CKD-EPI, FAS, and revised Lund-Malmö eGFR were 66, 72, 74, 71, and 67 mL/min/1.73m2, respectively. Overall, the r-LM had the highest CCC (0.83), lowest bias (-1.4 mL/min/1.73 m2), highest precision (16.2 mL/min/1.73 m2), and highest accuracy (P10â =â 39%). The RMAR (slope, intercept) in r-LM, FAS, MDRD, and CKD-EPI was 1.18, -13.35; 0.97, -2.9; 1, -6.4, and 1.04, -11.3, respectively. The Bland-Altman plot showed that r-LM had the lowest mean difference and the narrowest 95% limit of agreement (-1.0, 54.1 mL/min/1.73 m2), while mean difference was more than 5-fold higher in FAS, MDRD, and CKD-EPI (-5.2, -6.3, and -8.2, respectively). CONCLUSIONS: In adults with diabetes the revised Lund-Malmö performs better than MDRD, CKD-EPI, and FAS in calculating point estimates of GFR.
Subject(s)
Creatinine/blood , Diabetes Mellitus , Diabetic Nephropathies/diagnosis , Glomerular Filtration Rate , Adult , Aged , Algorithms , Creatinine/analysis , Diabetes Mellitus/blood , Diabetes Mellitus/diagnosis , Diabetes Mellitus/physiopathology , Diabetes Mellitus/urine , Diabetic Nephropathies/blood , Diabetic Nephropathies/urine , Female , Glycated Hemoglobin/analysis , Glycated Hemoglobin/metabolism , Humans , Male , Middle Aged , Models, Theoretical , Predictive Value of Tests , Renal Insufficiency, Chronic/blood , Renal Insufficiency, Chronic/diagnosis , Renal Insufficiency, Chronic/physiopathology , Renal Insufficiency, Chronic/urine , Reproducibility of ResultsABSTRACT
We previously described the discovery of Big angiotensin-25 (Bang-25), an angiotensin-related peptide isolated from human urine. Bang-25 consists of the first 25 amino acids of the N-terminus of angiotensinogen (Aogen), with N-linked glycosylation on the 14th amino acid and a cysteine conjugated to the 18th amino acid. Bang-25 is rapidly converted into angiotensin II (Ang II) by chymase. Because Bang-25 is widely distributed in human tissues, including islet cells in the pancreas and podocytes in the kidney, we hypothesized that it may participate in the Ang II production system in these tissues. To test this hypothesis, we developed a specific assay for Bang-25 and used it to examine the urinary concentrations of Bang-25 in patients with diabetes mellitus (DM). The assay used the Amplified Luminescent Proximity Homogeneous Assay (Alpha)-based ELISA method (AlphaLISA) of PerkinElmer Japan and included antibodies specific to the N-terminus of Ang II and the C-terminus of Bang-25. The AlphaLISA ImmunoAssay specifically recognized Bang-25 and had no cross-reactivity with Aogen or Ang I. Bang-25 was detected in healthy volunteers' urine samples but not in their plasma samples. In patients with DM, the urinary Bang-25 concentration was significantly higher than in healthy volunteers. Moreover, the results indicated that the Bang-25 concentration in the urine may offer a different perspective on disease status from that provided by urinary albumin. This assay could provide a useful tool for determining urinary Bang-25, which may prove an important biomarker for diabetic kidney disease.
Subject(s)
Angiotensin II/urine , Diabetes Mellitus/urine , Enzyme-Linked Immunosorbent Assay/methods , Adult , Female , Humans , Male , Middle AgedABSTRACT
BACKGROUND: The phenotype of diabetic kidney disease represents a lower estimated glomerular filtration rate (eGFR) and albuminuria. We investigated the association between day-by-day home blood pressure (BP) variability and the eGFR in subjects with diabetes and compared this association with that in subjects without diabetes. We then attempted to determine whether the association is present in albuminuria. METHODS: We analyzed 4,231 patients with risk factors of cardiovascular disease (24.4% with diabetes) from the J-HOP (Japan Morning Surge-Home Blood Pressure) study. Home BP was measured in the morning and evening for 14 days. We calculated the SD, coefficient of variation, average real variability (ARV), and variation independent of the mean of the subjects' morning and evening home systolic BP (SBP) as the indexes of day-by-day home BP variability. RESULTS: A multiple linear regression analysis adjusted for covariates showed both average morning and evening SBP were associated with the log-transformed urine albumin-to-creatinine ratio (UACR) with and without diabetes (all P < 0.05), but not with the eGFR except for an association of average evening SBP in the no-diabetes group. None of the indexes of day-by-day morning and evening home SBP variability were associated with the log-transformed UACR except for the association between the ARV of home morning SBP in the diabetes group. All of the indexes of day-by-day morning and evening home SBP variability were associated with the eGFR only in the diabetes group (all P < 0.05). CONCLUSIONS: The association between increased day-by-day home BP variability and impaired renal function was unique in diabetes.
Subject(s)
Albuminuria/physiopathology , Blood Pressure/physiology , Diabetes Mellitus/physiopathology , Diabetic Nephropathies/physiopathology , Glomerular Filtration Rate/physiology , Aged , Albuminuria/urine , Blood Pressure Monitoring, Ambulatory , Case-Control Studies , Creatinine/urine , Diabetes Mellitus/urine , Diabetic Nephropathies/urine , Female , Humans , Male , Middle AgedABSTRACT
BACKGROUND AND AIMS: Phenols and parabens are ubiquitous and have been associated with markers of cardiovascular health. However, the literature lacks population-based studies examining the link between these endocrine disruptors and diabetes. We examined the association between paraben/phenol concentrations and diabetes among a nationally representative sample of US adults. METHODS AND RESULTS: We utilized data from the 2005-2014 National Health and Nutrition Examination Surveys (N = 8498). Total urinary concentrations of BPA, triclosan, BP-3, and propyl, butyl, ethyl, and methyl parabens were measured from urine specimens collected during the examination session. Diabetes status was based on self-report of a previous diagnosis or HbA1c≥6.5%. We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CI) associated with the difference in log-transformed values of the 75th and 25th percentiles for each phenol/paraben, adjusting for potential confounders. The adjusted ORs (95% CI) of diabetes comparing the 75th to 25th percentiles of each paraben/phenol were 1.09 (0.96-1.23) for BPA, 0.84 (0.72-0.98) for triclosan, 0.69 (0.61-0.79) for BP-3, 0.71 (0.61-0.83) for propyl paraben, 0.66 (0.54-0.80) for butyl paraben, 0.60 (0.51-0.71) for ethyl paraben, and 0.79 (0.68-0.91) for methyl paraben. CONCLUSIONS: Higher concentrations of triclosan, BP-3, and propyl, butyl, ethyl, and methyl parabens were associated with lower odds of diabetes. These findings warrant further investigation into the potential mechanism behind the observed associations and the temporal direction of the associations, given that we cannot rule out reverse causation. Future studies of these endocrine disruptors may improve the understanding of their relationship with diabetes.
Subject(s)
Diabetes Mellitus/epidemiology , Diabetes Mellitus/urine , Endocrine Disruptors/urine , Parabens/metabolism , Phenols/urine , Biomarkers/urine , Cross-Sectional Studies , Diabetes Mellitus/diagnosis , Endocrine Disruptors/adverse effects , Female , Humans , Male , Middle Aged , Nutrition Surveys , Parabens/adverse effects , Phenols/adverse effects , Risk Assessment , Risk Factors , United States/epidemiologyABSTRACT
Purpose: The aim of the study was to investigate the prevalence and risk factors of diabetes mellitus (DM) in primary aldosteronism (PA) patients. Methods: This case-control study enrolled 259 PA patients in West China Hospital, China from January 2016 to January 2019. Patients were divided into three groups: PA group, PA + impaired fasting glucose (IFG)/impaired glucose tolerance (IGT) group and PA + DM group. Clinical characteristics (like age and sex) and laboratory variables (like plasma aldosterone concentration and plasma renin activity) were compared between three groups. Univariate and multivariate logistic regression analyses were performed to determine risk factors for DM in PA patients. The association of random blood glucose with the above-mentioned factors were also investigated by Pearson correlation analyses. Nomogram model was developed to predict the probability of DM in PA patients. Results: 49 (18.9%) patients were diagnosed with DM and 22 (8.5%) with IFG/IGT in 259 PA patients. Apart from older age, male, higher body mass index, higher triglycerides and lower cholesterol, we found that higher blood urea nitrogen (BUN) and higher 24 h urinary calcium (Ca) might be potential new risk factors for dysglycemia. The nomogram model for DM in PA patients had a good predictive accuracy, with the area under the curve of receiver operating characteristic of 0.839 (95% CI 0.784-0.893). Conclusions: PA patients were more likely to have DM compared with general population. Apart from older age, overweight and dyslipidemia, higher BUN and excessive excretion of urinary Ca may also be the new potential risk factors for DM in PA patients.
Subject(s)
Blood Urea Nitrogen , Calcium/urine , Diabetes Mellitus/etiology , Hyperaldosteronism/blood , Hyperaldosteronism/urine , Adult , Aged , Case-Control Studies , Diabetes Mellitus/blood , Diabetes Mellitus/epidemiology , Diabetes Mellitus/urine , Female , Humans , Hyperaldosteronism/complications , Hyperaldosteronism/epidemiology , Male , Middle Aged , Prediabetic State/blood , Prediabetic State/epidemiology , Prediabetic State/urine , Prevalence , Retrospective Studies , Risk Factors , UrinalysisABSTRACT
Alterations in sodium (Na+) relative to potassium (K+) intake increase systolic blood pressure, effects in-part attributed to enhanced pulsatile loads (pulse pressure) beyond steady-state pressures (mean arterial pressure). Whether this effect is through reversible changes (increases in blood volume and hence aortic flow [Q] or wave reflection [Pb]), or potentially irreversible structural changes in the proximal aorta, is unknown. In 581 black South Africans, we determined 24-hour urinary Na+ and K+ excretion and aortic function from central aortic pressure (radial pulse wave analysis [SphygmoCor software]), velocity, and diameter measurements. Proximal aortic function was assessed from characteristic impedance (Zc). Beyond mean arterial pressure and additional confounders, urinary Na+/K+ was independently associated with Zc (P<0.005) but not peak aortic Q (P=0.30) or alternative aspects of Q or ejection volume. Although age was strongly associated with proximal aortic diameter, no independent relations between urinary Na+/K+ and aortic diameter were noted (P=0.17). Relations between urinary Na+/K+ and Zc translated into independent relations with early systolic compression wave pressures (QxZc [PQxZc]) and aortic forward wave pressures but not Pb. Moreover, neither reflected wave magnitude (P=0.92) nor aortic pulse wave velocity were independently associated with urinary Na+/K+. In product of coefficient mediation analysis, the independent relations between urinary Na+/K+ and peak aortic or brachial pulse pressure or systolic blood pressure were accounted for by Zc and PQxZc. In conclusion, abnormalities in Na+/K+ intake determine pulse pressure or systolic blood pressure beyond mean arterial pressure mainly through potentially irreversible impacts on proximal aortic impedance rather than readily modifiable increases in aortic flow (blood volume) or wave reflection.
Subject(s)
Aorta/physiology , Arterial Pressure/physiology , Electric Impedance , Potassium/urine , Sodium/urine , Adult , Aged , Antihypertensive Agents/therapeutic use , Arterial Pressure/drug effects , Brachial Artery/physiology , Diabetes Mellitus/urine , Humans , Hypertension/drug therapy , Hypertension/physiopathology , Hypertension/urine , Middle Aged , Overweight/physiopathology , Overweight/urine , Recommended Dietary Allowances , Renin-Angiotensin System/physiology , Sodium Chloride Symporter Inhibitors/therapeutic use , Sodium Chloride, Dietary/adverse effects , Sodium Chloride, Dietary/pharmacology , Systole/physiology , Vascular ResistanceABSTRACT
To examine the association between urinary metabolites of polycyclic aromatic hydrocarbons (OH-PAHs) and diabetes, online databases, including PubMed, Scopus, and Web of Science, were searched on July 17, 2019. Of the 668 articles identified through searching, six cross-sectional studies involving 24,406 participants were included. The pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using a random-effect model. Heterogeneity was measured by reporting the I-square index. Moreover, subgroup analysis according to types of metabolites was performed. We found a significantly higher odds of diabetes in the highest versus the lowest category of urinary naphthalene (NAP), fluorine (FLU), phenanthrene (PHEN), and total OH-PAH metabolites. The pooled OR (95% CI) was estimated at 1.47 (1.17, 1.78), 1.50 (1.29, 1.71), 1.41 (1.21, 1.60), and 1.61 (1.01, 2.21), respectively. We also found a significant association per 1-fold increase in FLU (OR = 1.09, 95% CI [1.00, 1.19]) and PHEN (OR = 1.19, 95% CI [1.08, 1.30]) metabolites. In subgroup analysis stratified by types of OH-PAH metabolites, A significant stronger odds of diabetes was observed in the highest versus the lowest category of 2-PHEN (OR = 1.66, 95% CI [1.32, 2.00]), 2-NAP (OR = 1.66, 95% CI [1.16, 2.17]), 2-FLU (OR = 1.62, 95% CI [1.28, 1.97]), and 9-FLU (OR = 1.62, 95% CI [1.21, 2.04]) metabolites. Furthermore, there was a meaningfully greater likelihood of diabetes per 1-fold increase in 2-FLU (OR = 1.34, 95% CI [1.10, 1.57]), 2-PHEN (OR = 1.33, 95% CI [1.14, 1.51]), and 3-PHEN (OR = 1.19, 95% CI [1.04, 1.34]) metabolites. In conclusion, our study suggests the significant odds of association between urinary OH-PAH metabolites and diabetes.
Subject(s)
Diabetes Mellitus/urine , Polycyclic Aromatic Hydrocarbons/urine , Female , Fluorine/urine , Humans , Hydroxylation , Male , Naphthalenes/urine , Odds Ratio , Phenanthrenes/urine , Polycyclic Aromatic Hydrocarbons/metabolismABSTRACT
Paper-based analytical device (PAD) has received more and more attention in the field of point-of-care test (POCT) due to its low cost, portability and simple operation. Sensitivity and selectivity are two important aspects in clinical diagnostic analysis. However, low sensitivity of a PAD limits its wider application for POCT. Here we introduced a PAD that can clean and enrich the protein content from salty media with both electric field (E) and pH gradient (double E/pH gradients), with which 100-fold enrichment effect could be achieved within 70 s as demonstrated by fluorescein isothiocyanate labeled bovine serum albumin (FITC-BSA) from artificial urine media. With post staining of the protein stacking band with bromophenol blue (BPB), selective colorimetric detection of human serum albumin (HSA) was achieved simply with smartphone camera in the clinically significant range of 10-300 mgâ§L-1 (R2 = 0.99) with a limit of detection (LOD) of 4.9 mgâ§L-1. Detection of microalbuminuria (MAU) of diabetic patients was demonstrated with this method without difference (É = 0.01) to that by the clinical method (immunoturbidimetry). This work demonstrated the potential of this PAD method in online sample pretreatment and detection of target component from complex physiological samples.
Subject(s)
Microfluidic Analytical Techniques , Paper , Serum Albumin, Bovine/isolation & purification , Serum Albumin, Human/isolation & purification , Smartphone , Animals , Cattle , Diabetes Mellitus/diagnosis , Diabetes Mellitus/urine , Electromagnetic Fields , Humans , Hydrogen-Ion Concentration , Microfluidic Analytical Techniques/instrumentation , Salts/chemistry , Serum Albumin, Bovine/chemistry , Serum Albumin, Bovine/urine , Serum Albumin, Human/chemistry , Serum Albumin, Human/urineABSTRACT
OBJECTIVES: Diabetes is a global epidemic, and the high cost of annually and quantitatively measuring urine albumin excretion using the turbidimetric immunoassay is challenging. We aimed to determine whether a semi-quantitative urinary albumin-creatinine ratio test could be used as a screening tool for microalbuminuria in diabetic patients. METHODS: We assessed the diagnostic accuracy of the semi-quantitative method. The costs of false results in the semi-quantitative method were calculated based on the annual probability of disease progression analyzed through a systematic literature review and meta-analysis. The pooled long-term cost-saving effect of the semi-quantitative method compared with the quantitative test was assessed using a Markov model simulating a long-term clinical setting. Diagnostic accuracy and the cost-saving effect were also validated in an independent external cohort. RESULTS: Compared with the quantitative test, the semi-quantitative method had sensitivities of 93.5% and 81.3% and specificities of 61.4% and 63.1% in the overall sample of diabetic patients (n = 1,881) and in diabetic patients with eGFR ≥60 ml/min/1.73 m2 and a negative dipstick test (n = 1,110), respectively. After adjusting for direct and indirect medical costs, including the risk of disease progression, which was adjusted by the meta-analyzed hazard ratio for clinical outcomes, it was determined that using the semi-quantitative method could save 439.4 USD per person for 10 years. Even after adjusting the result to the external validation cohort, 339.6 USD could be saved for one diabetic patient for 10 years. CONCLUSIONS: The semi-quantitative method could be an appropriate screening tool for albuminuria in diabetic patients. Moreover, it can minimize the testing time and inconvenience and significantly reduce national health costs.
Subject(s)
Albuminuria/diagnosis , Diabetes Mellitus/urine , Diabetic Nephropathies/diagnosis , Diabetic Nephropathies/urine , Mass Screening/methods , Urinalysis/methods , Albuminuria/urine , Cohort Studies , Cost Savings/statistics & numerical data , Humans , Mass Screening/economics , Reproducibility of Results , Republic of Korea , Urinalysis/economics , Urinalysis/statistics & numerical dataABSTRACT
Exposure to 1-bromopropane (1-BP) has been reported to cause glutathione depletion and increase the level of oxidative damage, which play critical roles in diabetes. However, the possible associations or mechanisms of the exposure of 1-BP with the plasma glucose level and the risk of diabetes are unclear. In this study, we explored the relationships of the urinary 1-BP metabolite N-Acetyl-S-(n-propyl)-l-cysteine (BPMA) with fasting plasma glucose (FPG) levels and the risk of diabetes, and the mediating role of oxidative damage in the above relationships in 3678 urban adults from the Wuhan-Zhuhai cohort in China. We found a significant dose-response relationship between BPMA and FPG levels with a ß of 0.09 (95 % CI: 0.04, 0.14). In addition, mediating effect of urinary BPMA on FPG levels was observed depending on elevated 8-isoprostane level, with a median proportion of 32.06 %. Furthermore, we observed a significant association between urinary BPMA and the risk of diabetes, with an adjusted odds ratio of 1.34 (1.18, 1.52) for all participants. These results indicated that urinary 1-BP metabolites were positively associated with FPG levels and the risk of diabetes among urban adults in this cross-sectional study. Lipid peroxidation partially mediated the association between urinary 1-BP metabolites and FPG levels.