Prediction of microalbuminuria from proteinuria in chronic kidney disease due to non-diabetic lifestyle-related diseases: comparison with diabetes.

BACKGROUND: To suppress increases in kidney failure and cardiovascular disease due to lifestyle-related diseases other than diabetes, early intervention is desirable. We examined whether microalbuminuria could be predicted from proteinuria. METHODS: The participants consisted of adults who exhibited a urinary protein-to-creatinine ratio (uPCR) of < 0.5 g/gCr and an eGFR of ≥ 15 ml/min/1.73 m2 in their spot urine at their first examination for lifestyle-related disease. Urine was tested three times for each case, with microalbuminuria defined as a urinary albumin-to-creatinine ratio (uACR) of 30-299 mg/gCr, at least twice on three measurements. Youden's Index was used as an index of the cut-off value (CO) according to the ROC curve. RESULTS: A single uPCR was useful for differentiating normoalbuminuria and micro- and macroalbuminuria in patients with non-diabetic lifestyle-related diseases. Regarding the GFR categories, the CO of the second uPCR was 0.09 g/gCr (AUC 0.89, sensitivity 0.76, specificity 0.89) in G1-4 (n = 197) and 0.07 g/gCr (AUC 0.92, sensitivity 0.85, specificity 0.88) in G1-3a (n = 125). Using the sum of two or three uPCR measurements was more useful than a single uPCR for differentiating microalbuminuria in non-diabetic lifestyle disease [CO, 0.16 g/gCr (AUC 0.91, sensitivity 0.85, specificity 0.87) and 0.23 g/gCr (AUC 0.92, sensitivity 0.88, specificity 0.84), respectively]. CONCLUSION: Microalbuminuria in Japanese individuals with non-diabetic lifestyle-related diseases can be predicted from the uPCR, wherein the CO of the uPCR that differentiates normoalbuminuria and micro- and macroalbuminuria was 0.07 g/gCr for G1-3a, while that in G3b-4 was 0.09 g/gCr.

Renal and Cardiovascular Effects of SGLT2 Inhibition in Combination With Loop Diuretics in Patients With Type 2 Diabetes and Chronic Heart Failure: The RECEDE-CHF Trial.

BACKGROUND: SGLT2 (sodium-glucose cotransporter-2) inhibitors improve heart failure-associated outcomes in patients with type 2 diabetes. In patients with heart failure, SGLT2 inhibitors will likely be coprescribed with a loop diuretic, but this combined effect is not well-defined. Our aim was to assess the diuretic and natriuretic effect of empagliflozin in combination with loop diuretics. METHODS: The RECEDE-CHF trial (SGLT2 Inhibition in Combination With Diuretics in Heart Failure) was a randomized, double-blind, placebo-controlled, crossover trial of patients with type 2 diabetes and heart failure with reduced ejection fraction taking regular loop diuretic who were randomized to empagliflozin 25 mg once daily or placebo for 6 weeks with a 2-week washout period. The primary outcome was change in 24-hour urinary volume from baseline to week 6. RESULTS: Twenty-three participants (mean age, 69.8 years; 73.9% male; mean furosemide dose, 49.6±31.3 mg/d; mean HbA1c, 7.9±3.8%) were recruited. Compared with placebo, empagliflozin caused a significant increase in 24-hour urinary volume at both day 3 (mean difference, 535 mL [95% CI, 133-936]; P=0.005) and week 6 (mean difference, 545 mL [95% CI, 136-954]; P=0.005) after adjustment for treatment order, baseline 24-hour urine volume, and percentage change in loop diuretic dose. At 6 weeks, empagliflozin did not cause a significant change in 24-hour urinary sodium (mean difference, -7.85 mmol/L [95% CI, -2.43 to 6.73]; P=0.57). Empagliflozin caused a nonsignificant increase in fractional excretion of sodium at day 3, which was absent at week 6 (mean difference day 3, 0.30% [95% CI, -0.03 to 0.63]; P=0.09; week 6, 0.11% [95% CI, -0.22 to 0.44]; P>0.99), and a significant increase in electrolyte-free water clearance at week 6 (mean difference, 312 mL [95% CI, 26-598]; P=0.026) compared with placebo. Empagliflozin also caused significant reductions in body weight and serum urate at week 6. CONCLUSIONS: Empagliflozin caused a significant increase in 24-hour urine volume without an increase in urinary sodium when used in combination with loop diuretic. Registration: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT03226457.

Empagliflozin in Heart Failure: Diuretic and Cardiorenal Effects.

BACKGROUND: Sodium-glucose cotransporter-2 inhibitors improve heart failure-related outcomes. The mechanisms underlying these benefits are not well understood, but diuretic properties may contribute. Traditional diuretics such as furosemide induce substantial neurohormonal activation, contributing to the limited improvement in intravascular volume often seen with these agents. However, the proximal tubular site of action of the sodium-glucose cotransporter-2 inhibitors may help circumvent these limitations. METHODS: Twenty patients with type 2 diabetes mellitus and chronic, stable heart failure completed a randomized, placebo-controlled crossover study of empagliflozin 10 mg daily versus placebo. Patients underwent an intensive 6-hour biospecimen collection and cardiorenal phenotyping at baseline and again after 14 days of study drug. After a 2-week washout, patients crossed over to the alternate therapy with the above protocol repeated. RESULTS: Oral empagliflozin was rapidly absorbed as evidenced by a 27-fold increase in urinary glucose excretion by 3 hours (P<0.0001). Fractional excretion of sodium increased significantly with empagliflozin monotherapy versus placebo (fractional excretion of sodium, 1.2±0.7% versus 0.7±0.4%; P=0.001), and there was a synergistic effect in combination with bumetanide (fractional excretion of sodium, 5.8±2.5% versus 3.9±1.9%; P=0.001). At 14 days, the natriuretic effect of empagliflozin persisted, resulting in a reduction in blood volume (-208 mL [interquartile range, -536 to 153 mL] versus -14 mL [interquartile range, -282 to 335 mL]; P=0.035) and plasma volume (-138 mL, interquartile range, -379 to 154±453 mL; P=0.04). This natriuresis was not, however, associated with evidence of neurohormonal activation because the change in norepinephrine was superior (P=0.02) and all other neurohormones were similar (P<0.34) during the empagliflozin versus placebo period. Furthermore, there was no evidence of potassium wasting (P=0.20) or renal dysfunction (P>0.11 for all biomarkers), whereas both serum magnesium (P<0.001) and uric acid levels (P=0.008) improved. CONCLUSIONS: Empagliflozin causes significant natriuresis, particularly when combined with loop diuretics, resulting in an improvement in blood volume. However, off-target electrolyte wasting, renal dysfunction, and neurohormonal activation were not observed. This favorable diuretic profile may offer significant advantage in the management of volume status in patients with heart failure and may represent a mechanism contributing to the superior long-term heart failure outcomes observed with these agents. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03027960.

Urinary Amino-Terminal Pro-C-Type Natriuretic Peptide: A Novel Marker of Chronic Kidney Disease in Diabetes.

BACKGROUND: Chronic renal inflammation and fibrosis are common sequelae in diabetes mellitus (DM) and are major causes of premature mortality. Although upregulation of NPPC expression occurs in response to renal inflammation in experimental animals, nothing is known of the molecular forms of C-type natriuretic peptide (CNP) products in urine of people with DM or links with renal function. METHODS: ProCNP products in urine were characterized with HPLC and a range of antisera directed to specific epitopes of amino-terminal proCNP (NTproCNP). The 5-kDa intact peptide was quantified in spot urine samples from healthy adults and 202 participants with DM selected to provide a broad range of renal function. RESULTS: The predominant products of proCNP in urine were consistent with the 2-kDa fragment (proCNP 3-20) and a smaller peak of intact (5-kDa) fragment (proCNP 1-50, NTproCNP). No peaks consistent with bioactive forms (proCNP 82-103, 50-103) were identified. The urine NTproCNP to creatinine ratio (NCR) was more reproducible than the albumin to creatinine ratio (ACR) and strongly associated with the presence of chronic kidney disease. In models predicting independence, among 10 variables associated with renal function in DM, including plasma NTproCNP, only 3 (sex, ACR, and plasma creatinine) contributed to NCR. CONCLUSIONS: Characterization of the products of proCNP in urine confirmed the presence of NTproCNP. In spot random urine from study participants with DM, NCR is inversely associated with estimated glomerular filtration rate. In contrast to ACR, NCR reflects nonvascular factors that likely include renal inflammation and fibrosis.

Urinary 8-iso-prostaglandin F2α as a risk marker for the vulnerability of culprit plaque in diabetic patients with stable coronary artery disease.

We evaluated the association of urinary excretion of 8-iso-prostaglandin F2α (8-iso-PGF2α) with the vulnerability of culprit lesions in 156 age- and sex-matched diabetic stable coronary artery disease (CAD) patients with or without thin-capped fibroatheroma (TCFA) identified by iMAP intravascular ultrasound. Fasting urinary 8-iso-PGF2α level was measured and corrected by creatinine clearance. Compared to non-TCFA group, patients with TCFA had higher urinary 8-iso-PGF2α levels [114.6 (71.1, 181.5) vs. 83.0 (63.2, 138.2) pmol/mmolCr, P = 0.012]. Urinary 8-iso-PGF2α level was positively correlated with percent necrotic volume of culprit lesion (r = 0.218, P = 0.006). High urinary 8-iso-PGF2α level (OR 2.941, P = 0.009) was independently associated with the presence of TCFA and displayed a significant value in predicting TCFA plaques in study patients. The current study indicated that urinary 8-iso-PGF2α may be an important surrogate marker for the vulnerability of culprit lesion in diabetic patients with CAD.

Successful Diabetic Control as Measured by Hemoglobin A1c Is Associated with Lower Urine Risk Factors for Uric Acid Calculi.

INTRODUCTION AND OBJECTIVES: To examine the association of glycemic control, including strict glycemic control, with 24-hour urine risk factors for uric acid and calcium calculi. MATERIALS AND METHODS: With institutional review board (IRB) approval, we identified 183 stone formers (SFs) with 459 twenty-four-hour urine collections. Hemoglobin A1c (HgbA1c) measures were obtained within 3 months of the urine collection. Collections were categorized into normoglycemic (NG, HgbA1c < 6.5) and hyperglycemic (HG, HgbA1c ≥ 6.5) cohorts; 24-hour urine parameters were compared. The NG cohort was further divided into patients with and without a history of diabetes mellitus (DM) type 2. Variables were analyzed using chi-square, Welch's t-test and multivariate linear regression to adjust for clustering, body mass index (BMI), age, gender, thiazide use, and potassium citrate use. RESULTS: Patients in the HG group were older with higher BMI. Multivariate analysis of the total study population revealed that hyperglycemia correlated with lower pH, higher uric acid relative saturation (RS), lower brushite RS, and higher citrate. NG SFs with and without a history of DM had similar risk factors for uric acid stone formation. Among NG SFs, those with DM had higher urine calcium and calcium oxalate RS than those without DM. However, this difference may be related to other factors since neither parameter correlated with DM on multivariate regression (p > 0.05). CONCLUSIONS: Successful glycemic control may be associated with reduced urinary risk factors for uric acid stone formation. Patients with well-controlled DM had equivalent risk factors to those without DM. Glycemic control should be considered a target of the multidisciplinary medical management of stone disease.

Urine levels of 5-aminoimidazole-4-carboxamide riboside (AICAR) in patients with type 2 diabetes.

AIMS: 5-Aminoimidazole-4-carboxamide riboside (AICAR) is an endogenous activator of AMPK, a central regulator of energy homeostasis. Loss and/or reduction of AMPK signaling plays an important role in the development of insulin resistance in type 2 diabetes. The loss of AMPK in diabetes could be due to a loss of AICAR. The aim of this study was to characterize urine levels of AICAR in diabetes and determine whether an association exists with respect to late complications, e.g., retinopathy, nephropathy and neuropathy. METHODS: Urine AICAR was measured by liquid chromatography tandem mass spectrometry in 223 patients consisting of 5 healthy controls, 63 patients with pre-diabetes, 29 patients with newly diagnosed type 2 diabetes and 126 patients with long-standing type 2 diabetes. For statistical analyses, nonparametric Kruskal-Wallis test, one-way ANOVA and multivariate regression analysis were performed to investigate the associations of urinary AICAR excretion within different groups and different clinical parameters. RESULTS: The mean urine AICAR for all 223 patients was 694.7 ± 641.1 ng/ml. There was no significant difference in urine AICAR between the control and patients with diabetes (592.3 ± 345.1 vs. 697.1 ± 646.5 ng/ml). No association between any of the biochemical and/or clinical parameters measured and urine AICAR was found, with the exception of age of patient (R = - 0.34; p < 0.01) and estimated glomerular filtration rate (R = 0.19; p = 0.039). These results were confirmed additionally by linear regression analysis. CONCLUSIONS: Clinical diabetes is not associated with a change in endogenous AICAR levels. Loss of AICAR may therefore not be a mechanism by which AMPK signaling is reduced in diabetes.

DNA methylation profiling of genomic DNA isolated from urine in diabetic chronic kidney disease: A pilot study.

AIM: To characterise the genomic DNA (gDNA) yield from urine and quality of derived methylation data generated from the widely used Illuminia Infinium MethylationEPIC (HM850K) platform and compare this with buffy coat samples. BACKGROUND: DNA methylation is the most widely studied epigenetic mark and variations in DNA methylation profile have been implicated in diabetes which affects approximately 415 million people worldwide. METHODS: QIAamp Viral RNA Mini Kit and QIAamp DNA micro kit were used to extract DNA from frozen and fresh urine samples as well as increasing volumes of fresh urine. Matched buffy coats to the frozen urine were also obtained and DNA was extracted from the buffy coats using the QIAamp DNA Mini Kit. Genomic DNA of greater concentration than 20µg/ml were used for methylation analysis using the HM850K array. RESULTS: Irrespective of extraction technique or the use of fresh versus frozen urine samples, limited genomic DNA was obtained using a starting sample volume of 5ml (0-0.86µg/mL). In order to optimize the yield, we increased starting volumes to 50ml fresh urine, which yielded only 0-9.66µg/mL A different kit, QIAamp DNA Micro Kit, was trialled in six fresh urine samples and ten frozen urine samples with inadequate DNA yields from 0-17.7µg/mL and 0-1.6µg/mL respectively. Sufficient genomic DNA was obtained from only 4 of the initial 41 frozen urine samples (10%) for DNA methylation profiling. In comparison, all four buffy coat samples (100%) provided sufficient genomic DNA. CONCLUSION: High quality data can be obtained provided a sufficient yield of genomic DNA is isolated. Despite optimizing various extraction methodologies, the modest amount of genomic DNA derived from urine, may limit the generalisability of this approach for the identification of DNA methylation biomarkers of chronic diabetic kidney disease.

Bacterial Quality of Urinary Tract Infections in Diabetic and Non Diabetics of the Population of Ma'an Province, Jordan.

BACKGROUND AND OBJECTIVE: The patients with Diabetes Mellitus (DM) have malfunction in bladder which prompt urine accumulation in its pool which serves a decent situation to the microbes to be develop and cause Urinary Tract Infection (UTI). The UTI is the most infectious disease that affects both males and females. This study was designed to detect the bacterial species responsible for UTI in both diabetic and non-diabetic patients in Ma'an province, Jordan. MATERIALS AND METHODS: One hundred sixteen urine samples were investigated to determine UTI-causing bacteria. These samples distributed unequally between diabetic male (12) and diabetic female (25) and also non-diabetic male (13) and non-diabetic female (66). RESULTS: It was observed that E. coli is responsible for large proportion (44.8%) of UTI in both diabetic (15.5%) and non-diabetic (29.3%) patients. This study showed inequality in the bacterial species that were isolated from both diabetic and non-diabetic samples. However, five bacterial species including E. aerogenes, E. cloacae, C. freundii, A. baumannii and B. subtilis did not exist in all diabetic samples. Treatment of UTI in both diabetic and non-diabetic patients with chloramphenicol (30 µg), ciprofloxacin (5 µg) and vancomycin (30 µg) resulted in more favorability than other antibiotics. At the same time cephalothin (30 µg) was not recommended. CONCLUSION: Escherichia coli was the prevailing bacterial infections among those which were isolated from patients with UTI. Certain forms of bacterial infections inclined to be extra common in diabetic patients than others and other infections may be more severe in people with diabetics than in non diabetics.

Vitamin D and Albuminuria in Youth with and without Type 1 Diabetes.

BACKGROUND/AIMS: In adults, lower vitamin D has been associated with increased albuminuria. This association has not been extensively studied in youth with or without type 1 diabetes. METHODS: We examined the cross-sectional association between vitamin D and albuminuria (urine albumin to creatinine ratio ≥30 mg/g) in 8,789 participants of the National Health and Nutrition Survey 2001-2006 (NHANES), who were 6-19 years old. Further, we examined the association between vitamin D and albuminuria in 938 participants from the SEARCH Nutritional Ancillary Study (SNAS), a longitudinal cohort of youth with type 1 diabetes. RESULTS: Of the NHANES participants, 5.3, 19.5, and 53.7% had vitamin D levels <30, 50 and 80 nmol/L, respectively. Albuminuria was present in 12.8% and was more common in younger children, females, non-Hispanic whites, non-obese children, and children with hypertension. After adjustments, there was no association between vitamin D and albuminuria. Among the SNAS participants with type 1 diabetes, we also found no association between baseline vitamin D and subsequent albuminuria in unadjusted or adjusted analyses. CONCLUSION: We did not find an association between serum vitamin D and albuminuria in either non-diabetic youth or those with type 1 diabetes. Further research is needed to more fully understand this relationship.

Serum klotho protein levels and their correlations with the progression of type 2 diabetes mellitus.

AIM: To investigate the associations of serum α-Klotho and ß-Klotho levels with type 2 diabetes mellitus (T2DM) progression. METHODS: We evaluated 106 healthy controls and 261 cases of T2DM with or without diabetic complications (range: 45-84years). Serum α-Klotho and ß-Klotho levels were analyzed using enzyme-linked immunosorbent assays. RESULTS: Compared to the healthy controls, α-Klotho and ß-Klotho levels were significantly lower among patients with T2DM and with or without diabetic complications (P<0.05). Furthermore, α-Klotho levels were lower in the microalbuminuric and macroalbuminuric groups, compared to the normoalbuminuric group. However, ß-Klotho levels were only lower in the macroalbuminuric group (P<0.05). Multiple linear regression analyses revealed that α-Klotho and ß-Klotho levels were positively correlated with the creatinine clearance rate, and negatively correlated with the urinary albumin to creatinine ratio and randomly sampled serum levels of creatinine, blood urea nitrogen, and blood glucose. Moreover, α-Klotho and ß-Klotho levels were positively correlated among patients with T2DM (r=0.693, P<0.001). CONCLUSIONS: Serum levels of α-Klotho and ß-Klotho are down-regulated in patients with T2DM. Thus, these proteins may participate in the pathological mechanism of diabetes, and the positive correlation of α-Klotho and ß-Klotho levels indicates that they might have similar mechanisms in T2DM.

Associations between urinary kidney injury biomarkers and cardiovascular mortality risk in elderly men with diabetes.

AIM: Three urinary biomarkers, kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and cystatin C, have been suggested as clinically relevant highly specific biomarkers of acute kidney tubular damage. Yet, the utility of these biomarkers in the prognostication of diabetic nephropathy has been less studied. Therefore, we aimed to investigate the longitudinal association between these urinary biomarkers and cardiovascular mortality in patients with diabetes. METHODS: The study sample consisted of participants with diabetes in the community-based Uppsala Longitudinal Study of Adult Men (n = 91; mean age 77.8 years). During follow-up (median 8.3 years, interval 0.7-13.4 years), 33 participants died of cardiovascular causes. RESULTS: In a multivariable Cox regression model adjusting for age, glomerular filtration rate, and urinary albumin/creatinine ratio, higher urinary KIM-1/creatinine was associated with an increased risk for cardiovascular mortality (HR per SD increase 1.51, 95% confidence intervals 1.03-2.24, P = 0.03). Neither urinary NGAL/creatinine nor urinary cystatin C/creatinine were independently associated with an increased cardiovascular mortality risk. CONCLUSION: In elderly men with diabetes, higher urinary KIM-1/creatinine was associated with an increased long-term risk of cardiovascular mortality independently of established markers of diabetic nephropathy. Our data provide support for kidney tubular damage as an important aspect of diabetic nephropathy that merits further investigation.

Emphysematous pyelitis and cystitis associated with vesicoureteral reflux in a diabetic dog.

A 12-year-old female dog with a 3-month history of poor response to diabetes treatment had an acute worsening of symptoms, including weakness and blindness. The dog had elevated blood glucose, alkaline phosphatase and urea concentration, hyposthenuria, glycosuria, hematuria, and pyuria. Escherichia coli was isolated from the urine. Radiographs and ultrasound examination showed that the dog had unilateral emphysematous pyelitis and concurrent cystitis associated with vesicoureteral reflux.

Pyélite emphysémateuse et cystite associées au reflux vésico-urétéral chez une chienne diabétique. Une chienne âgée de 12 ans avec une anamnèse de 3 mois de mauvaise réponse au traitement du diabète a présenté un aggravement aigu des symptômes, y compris de la faiblesse et de la cécité. La chienne avait une glycémie élevée, ainsi que des concentrations sériques élevées de la phosphatase alcaline et d'urée, de l'hyposthénurie, de la glycosurie, de l'hématurie et de la pyurie. Escherichia coli a été isolé de l'urine. Des radiographies et des échographies ont montré que la chienne était atteinte de pyélite emphysémateuse unilatérale et de cystite concomitante associées au reflux vésico-urétéral.(Traduit par Isabelle Vallières).

Glomerular Filtration Rate and Urine Albumin to Creatinine Ratio Associated With Hearing Impairment Among Korean Adults With Diabetes: A Nationwide Population-Based Study.

The objective of this study was to examine the association of estimated glomerular filtration rate (eGFR) and urine albumin to creatinine ratio (ACR) with hearing impairment among diabetic adults in Korea. The study was based on data from Korea National Health and Nutrition Examination Survey 2011 to 2012. Participants were 1206 diabetic adults, aged over 19 years, who completed audiometric testing supervised by nationally certified clinicians. Hearing impairment was defined in three grades: no hearing impairment (pure-tone average 0-25 dB), slight hearing impairment (26-40 dB), and disabling hearing impairment (>40 dB) in the better ear at frequencies 0.5, 1, 2, 3, 4 and 6 kHz. Using logistic regression, risk of hearing impairment was assessed after having controlled for confounding factors. Higher levels of ACR and lower levels of eGFR correlated with an increase in percentage of disabling hearing impairment both unilaterally and bilaterally (P < 0.001). Controlling for possible confounding covariates, odds ratios for hearing impairment showed tendency to increase in higher ACR groups (P for trend = 0.029). Similar pattern was examined between eGFR and hearing impairment (P for trend = 0.006). Odds ratios were 1.981 (1.146, 3.424) for ACR Q4 and 2.773 (1.286, 5.983) for eGFR < 60 mL/min. Fall in eGFR and rise in ACR correlated with severity of hearing impairment. The association existed independently of age, sex, body mass index (BMI), smoking, drinking, exercise, new onset of diabetes, education, income, mental stress, noise exposure, and metabolic syndrome.

Bacterial resistance in urinary tract infections in patients with diabetes matched with patients without diabetes.

BACKGROUND: With bacterial resistances having increased, patients with diabetes who are at higher risk of urinary tract infection (UTI) need to be studied. The study aim was to compare bacterial resistances to ofloxacin, cefixim, co-trimoxazole, nitrofurantoin and fosfomycin in UTI between patients with and without diabetes. METHODS: A cross-sectional study was conducted in ambulatory laboratories, including patients over 18 coming for urinalyses. Patients with diabetes were matched with two patients without diabetes based on risk factors for UTI using a propensity score. RESULTS: Among 1119 patients with UTI, 124 patients with diabetes were matched with 246 patients without diabetes. In patients with diabetes, the bacteria identified were: Escherichia coli (71%), Klebsiella (6%), Staphylococcus (5%), Enterococcus (4%), Proteus (2%) and Pseudomonas (1%); these findings were similar to those found in patients without diabetes. Resistances to ofloxacin and cefixim regardless of the bacteria were increased in patients with diabetes after matching on age, sex and history of UTI (respectively: OR=2.09; p=0.04 and OR=3.67; p=0.05). Regarding E. coli resistance, there was no difference whatever the antibiotic. CONCLUSION: The increased ofloxacin and cefixim resistance in patients with diabetes should be considered when prescribing probabilistic antibiotics, and could lead to changes in first-line treatments in UTI.

Elevated Levels of Urinary Markers of Oxidative DNA and RNA Damage in Type 2 Diabetes with Complications.

The mechanisms underlying progression of type 2 diabetes are complex and varied. Recent studies indicated that oxidative stress provided a new sight. To further assess the relationship between nucleic acid oxidation and complications in patients with type 2 diabetes and explore its possible molecular mechanisms, we studied 1316 subjects, including 633 type 2 diabetes patients and 683 age- and sex-matched healthy controls. Urinary levels of DNA oxidation marker 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) and RNA oxidation marker 8-oxo-7,8-dihydroguanosine (8-oxoGuo) were measured by ultraperformance liquid chromatography and mass spectrometry (UPLC-MS/MS). Serum glucose, HbA1c, total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides (TG) were also determined. The results showed significantly elevated levels of both the urinary 8-oxodGuo and 8-oxoGuo in diabetes patients with/without complications compared with age-matched healthy control subjects (p = 0.02 and p < 0.001, resp.). Patients with complications, especially macrovascular complications, exhibited higher levels of 8-oxoGuo than those without complications, while there was no difference in the concentrations of serum glucose and lipids. The finding indicates the role for oxidative damage to DNA and RNA, as a molecular mechanism contributing to the progression of type 2 diabetes. Elevated levels of 8-oxoGuo may be a risk factor for type 2 diabetes complications, especially in diabetic macrovascular complications.

[The test-system for detection of microalbuminuria using the new recombinant albumin-bounded poly-peptide].

The diabetes mellitus and arterial hypertension are among the most significant pathologies conditioning disorder of excretion of protein with urine. These very diseases are mostly dangerous for kidneys. Therefore, important significance has the search of early manifestations of damage of kidneys in patients with these diseases. The microalbuminuria is one of early manifestations of affection of kidneys in patients with diabetes mellitus and arterial hypertension. Only this early (pre-clinical) stage of affection of kidneys is the only reversible one in case of prescription of medicinal therapy. Nowadays, factually all applied diagnostic test-systems for detection ofmicroalbuminuria are based on immunological half-quantitative and quantitative detection of concentration of human serum albumin in urine. In this study was applied new recombinant human serum poly-peptide A3 from strain of streptococcus group G isolated from cow milk. The human serum albumin-binding capacity of poly-peptide A3 was analyzed in comparison with poly-peptide A2. Previously, recombinant human serum albumin-binding poly-peptide A2 was primarily applied in test-system for detection of microalbuminuria instead of commonly used antibodies. The analysis of 'human serum albumin-binding capacity of recombinant human serum poly-peptide A3 and A2 demonstrated that both of them can interact with human serum albumin in solution and adsorbed condition. This characteristic permitted applying poly-peptide A3 in immobilized form in qualitative test-system for detecting microalbuminuria. The actual study also propose specific and sensitive technique of screening and monitoring of patients with diabetes mellitus and arterial hypertension. The mentioned technique used tagged human serum albumin-binding polypeptide A3 combined with microchip technology. The comparison of test-systems using recombinant poly-peptides A3 and A2 established that application of poly-peptide A3 in test-system permits to detect more precisely concentration of human serum albumin in urine samples. The test-system of this kind was successfully implemented for both detection and qualitative identification of microalbuminuria in patients with diabetes mellitus and arterial hypertension.

Urinary loss of micronutrients in diabetic patients attending a tertiary hospital servisse / Pérdida urinaria de micronutrientes en pacientes diabéticos atendidos en un hospital de tercer nivel

Background/aims: micronutrient deficiency may contribute to a poorer control of diabetes. Thus, the objective of the present study was to assess the urinary excretion of micronutrients in patients with type 2 diabetes mellitus. Methods: patients with diabetes and controls were assessed regarding food intake, anthropometry, urinary loss of micronutrients and compared by the nonparametric Mann-Whitney test (p<0.05). Results: nine diabetic volunteers (52±14 years, BMI 30±11 kg/m² and abdominal circumference (AC) of 99±25 cm) and 9 control individuals (51±16 years, BMI 26±5 kg/m² and AC of 90±13 cm) were studied. Higher iron excretion was observed in the diabetic group and higher magnesium excretion in the control group. Conclusions: the type 2 diabetic patients here studied did not show increased micronutrient excretion in urine when compared to controls (AU)

Introducción/objetivos: la deficiencia de micronutrientes puede contribuir a un menor control de la diabetes. El objetivo de este estudio fue evaluar la excreción urinaria de micronutrientes en pacientes con diabetes mellitus tipo 2. Métodos: los pacientes con diabetes y los controles fueron evaluados por la ingesta de alimentos, la antropometría, la pérdida urinaria de micronutrientes y comparados por Mann Whitney no paramétrico (p<0,05). Resultados: fueron evaluados nueve sujetos diabéticos (52±14 años con un IMC de 30±11 kg/m² y la circunferencia de la cintura (CC) de 99±25 cm) y nueve sujetos control (51±16 años, IMC 26±5 kg/m² y CA total de 90±13 cm). La excreción de hierro más alta se observó en el grupo diabético y la mayor excreción de magnesio en el grupo de control. Conclusiones: el tipo 2 de pacientes diabéticos estudiados aquí no mostraron un aumento en la excreción de micronutrientes en la orina en comparación con los controles (AU)

Differences in 24-h urine composition between nephrolithiasis patients with and without diabetes mellitus.

OBJECTIVES: To examine the differences in 24-h urine composition between nephrolithiasis patients with and without diabetes mellitus (DM) in a large cohort of stone-formers and to examine differences in stone composition between patients with and without DM. PATIENTS AND METHODS: A retrospective review of 1117 patients with nephrolithiasis and a 24-h urine analysis was completed. Univariable analysis of 24-h urine profiles and multivariable linear regression models were performed, comparing patients with and without DM. A subanalysis of patients with stone analysis data available was performed, comparing the stone composition of patients with and without DM. RESULTS: Of the 1117 patients who comprised the study population, 181 (16%) had DM and 936 (84%) did not have DM at the time of urine analysis. Univariable analysis showed significantly higher total urine volume, citrate, uric acid (UA), sodium, potassium, sulphate, oxalate, chloride, and supersaturation (SS) of UA in individuals with DM (all P < 0.05). However, patients with DM had significantly lower SS of calcium phosphate and pH (all P < 0.05). Multivariable analysis showed that patients with DM had significantly lower urinary pH and SS of calcium phosphate, but significantly greater citrate, UA, sulphate, oxalate, chloride, SSUA, SS of calcium oxalate, and volume than patients without DM (all P < 0.05). Patients with DM had a significantly greater proportion of UA in their stones than patients without DM (50.2% vs 13.5%, P < 0.001). CONCLUSIONS: DM was associated with multiple differences on 24-h urine analysis compared with those without DM, including significantly higher UA and oxalate, and lower pH. Control of urinary UA and pH, as well as limiting intake of dietary oxalate may reduce stone formation in patients with DM.

[Periodontal disease in children with diabetes mellitus type 1].

The aim of the article was to study the occurrence of periodontal diseases in children with type I diabetes mellitus. The examination of 78 children revealed periodontal diseases in 40 children with type I diabetes. OHI-S, CPITN, PMA indices were determined. Pathological changes in periodontal tissues were revealed in 100% of cases. The following were identified: gingival hemorrhage (100%), over - and under-gingival dental tartar (100%), inflammation of gingival papilla (87,5%) marginal (80%) and alveolar gingiva (55%). Spread of periodontal disease among children with I type diabetes is characterized as high and is equal to 100%. Degree of periodontal sickness is evaluated as average and is M=2,28; SD=0,47 according to CPITN index. Treatment and preventive measures should be carried out taking into account major somatic disease.