Management of hypertension and renin-angiotensin-aldosterone system blockade in adults with diabetic kidney disease: Association of British Clinical Diabetologists and the Renal Association UK guideline update 2021.

People with type 1 and type 2 diabetes are at risk of developing progressive chronic kidney disease (CKD) and end-stage kidney failure. Hypertension is a major, reversible risk factor in people with diabetes for development of albuminuria, impaired kidney function, end-stage kidney disease and cardiovascular disease. Blood pressure control has been shown to be beneficial in people with diabetes in slowing progression of kidney disease and reducing cardiovascular events. However, randomised controlled trial evidence differs in type 1 and type 2 diabetes and different stages of CKD in terms of target blood pressure. Activation of the renin-angiotensin-aldosterone system (RAAS) is an important mechanism for the development and progression of CKD and cardiovascular disease. Randomised trials demonstrate that RAAS blockade is effective in preventing/ slowing progression of CKD and reducing cardiovascular events in people with type 1 and type 2 diabetes, albeit differently according to the stage of CKD. Emerging therapy with sodium glucose cotransporter-2 (SGLT-2) inhibitors, non-steroidal selective mineralocorticoid antagonists and endothelin-A receptor antagonists have been shown in randomised trials to lower blood pressure and further reduce the risk of progression of CKD and cardiovascular disease in people with type 2 diabetes. This guideline reviews the current evidence and makes recommendations about blood pressure control and the use of RAAS-blocking agents in different stages of CKD in people with both type 1 and type 2 diabetes.

Association of Urinary Sodium Excretion and Left Ventricular Hypertrophy in People With Type 2 Diabetes Mellitus: A Cross-Sectional Study.

Background: It has been well documented that left ventricular hypertrophy (LVH) is highly associated with the incidence of cardiovascular disease (CVD). Evidence indicated that high sodium intake was closely related with LVH in general population. However, information is not available regarding the association between urinary sodium excretion and LVH in patients with type 2 diabetes mellitus (T2DM). This study aimed to explore the association between urinary sodium excretion and LVH in patients with T2DM. Methods: This cross-sectional analysis included baseline data from 1,556 individuals with T2DM enrolled in the NanFang Prospective Diabetes Study (NFPDS). Urinary sodium excretion levels were measured from 24-hour urine samples of inpatients and morning fasting urine samples of outpatients. Left ventricular dimensions were assessed by echocardiography. The associations between urinary sodium excretion and the risks of cardiovascular events, LVH and left ventricular mass index (LVMI) were examined using linear regression analysis, logistic regression and restricted cubic splines (RCS). Results: Urinary sodium excretion levels were positively associated with cardiometabolic risk factors, including systolic blood pressure, body mass index, waist circumference and LVMI (All P<0.001). Odds ratios of the highest quartile of urinary sodium excretion compared with the lowest quartile were 1.80 (95% CI, 1.28-2.54; P=0.001) for LVH and 1.77 (95% CI, 1.06-2.94; P=0.028) for CVD, after adjusted for demographics, lifestyle risk factors and cardiovascular risk factors. Multivariable-adjusted RCS analysis of the association between urinary sodium excretion and LVMI showed a significant association (P=0.001) and lacked evidence of a nonlinear association (P=0.406). Conclusion: This study indicated that high urinary sodium excretion was independently associated with increased risk of LVH and CVD in patients with T2DM, suggesting that control of sodium intake may be valuable for the prevention of diabetic cardiovascular complications.

Associations between urinary 6-sulfatoxymelatonin excretion and diabetic vascular complications or arteriosclerosis in patients with type 2 diabetes.

AIMS/INTRODUCTION: There are limited reports on the association between melatonin levels and vascular complications in patients with type 2 diabetes. The aim of this study was to determine the association between urinary 6-sulfatoxymelatonin, which is a urinary metabolite of melatonin, and diabetic vascular complications or arteriosclerosis in patients with type 2 diabetes. MATERIALS AND METHODS: This retrospective study included patients (167 patients with type 2 diabetes and 27 patients without diabetes adjusted for age and sex) admitted to the hospital who underwent measurement of urinary 6-sulfatoxymelatonin. The urinary 6-sulfatoxymelatonin/creatinine ratio (6-SMT) was calculated. RESULTS: The natural logarithmically scaled 6-SMT level (Ln 6-SMT) was significantly lower in type 2 diabetes patients (1.9 ± 1.1) compared with patients without diabetes (2.8 ± 1.0, P < 0.001). Multivariate linear regression analysis identified duration of diabetes, smoking status, urinary albumin-to-creatinine ratio, retinopathy and coronary heart disease as factors that could influence Ln 6-SMT levels in type 2 diabetes patients (R2  = 0.232, P < 0.001). Ln 6-SMT was associated with decreased odds of diabetic retinopathy, even after adjustment for various confounding factors (odds ratio 0.559, 95% confidence interval 0.369-0.846, P = 0.006). Similarly, Ln 6-SMT was associated with decreased odds of coronary heart disease (odds ratio 0.442, P = 0.030). CONCLUSIONS: Our results showed the presence of low levels of Ln 6-SMT in type 2 diabetes patients relative to patients without diabetes. Furthermore, Ln 6-SMT is an independent risk factor of diabetic retinopathy and coronary heart diseases. These findings suggest that 6-SMT could be a useful biomarker for the prediction of micro- and macrovasculopathies in patients with type 2 diabetes.

Association of Urine Haptoglobin With Risk of All-Cause and Cause-Specific Mortality in Individuals With Type 2 Diabetes: A Transethnic Collaborative Work.

OBJECTIVE: Haptoglobin is an acute-phase reactant with pleiotropic functions. We aimed to study whether urine haptoglobin may predict risk of mortality in people with type 2 diabetes. RESEARCH DESIGN AND METHODS: We employed a transethnic approach with a cohort of Asian origin (Singapore) (N = 2,061) and a cohort of European origin (France) (N = 1,438) included in the study. We used survival analyses to study the association of urine haptoglobin with risk of all-cause and cause-specific mortality. RESULTS: A total of 365 and 525 deaths were registered in the Singapore cohort (median follow-up 7.5 years [interquartile range 3.5-12.8]) and French SURDIAGENE cohort (median follow-up 6.8 years [interquartile range 4.3-10.5], respectively. Singapore participants with urine haptoglobin in quartiles 2 to 4 had higher risk for all-cause mortality compared with quartile 1 (unadjusted hazard ratio [HR] 1.47 [95% CI 1.02-2.11], 2.28 [1.62-3.21], and 4.64 [3.39-6.35], respectively). The association remained significant in quartile 4 after multiple adjustments (1.68 [1.15-2.45]). Similarly, participants in the French cohort with haptoglobin in quartile 4 had significantly higher hazards for all-cause mortality compared with quartile 1 (unadjusted HR 2.67 [2.09-3.42] and adjusted HR 1.49 [1.14-1.96]). In both cohorts, participants in quartile 4 had a higher risk of mortality attributable to cardiovascular disease and infection but not malignant tumor. CONCLUSIONS: Urine haptoglobin predicts risk of mortality independent of traditional risk factors, suggesting that it may potentially be a novel biomarker for risk of mortality in patients with type 2 diabetes.

MiRNA Expression is Associated with Clinical Variables Related to Vascular Remodeling in the Kidney and the Brain in Type 2 Diabetes Mellitus Patients.

Background: The association of vascular remodeling in the kidney and the brain with a particular microRNAs (miRNA) profile is not well studied.Methods: Seventy-six patients with Type 2 diabetes and 11 healthy subjects were assessed concerning urine albumin: creatinine ratio (UACR), biomarkers of podocyte injury and of proximal tubule (PT) dysfunction. MiRNA were quantified in blood and urine by a real-time PCR System. Cerebrovascular ultrasound measurements were performed in the carotid and middle cerebral arteries.Results: MiRNA21 and miRNA124 correlated positively with nephrin, podocalyxin, synaptopodin, urinary N-acetyl-D-glucosaminidase (NAG), urinary kidney-injury molecule-1 (KIM-1), UACR, and negatively with eGFR; miRNA125a, 126, 146a, 192 correlated negatively with nephrin, podocalyxin, synaptopodin, urinary NAG, urinary KIM-1, UACR, and directly with eGFR. Plasma miRNA-21 and miRNA192 correlated directly with cerebral hemodynamics parameters of atherosclerosis and arteriosclerosis. MiRNA-124, 125a, 126, 146a showed negative correlations with the same parameters.Conclusions: In Type 2 diabetes patients there is an association of vascular remodeling in the brain and the kidney with a specific miRNAs pattern. Cerebrovascular changes occur even in normoalbuminuric patients, with 'high-to-normal' levels of podocyte injury and PT dysfunction biomarkers. These phenomena may be explained by the variability of miRNA expression within the two organs in early DKD.

Reduction in albuminuria with dapagliflozin cannot be predicted by baseline clinical characteristics or changes in most other risk markers.

The sodium glucose co-transporter-2 inhibitor dapagliflozin has been shown to decrease urinary albumin-to-creatinine ratio (UACR). This effect, however, varies among individual patients. In this study, we assessed the baseline characteristics and concurrent changes in other cardiovascular risk markers that might be associated with UACR response to dapagliflozin. A pooled analysis of 11 phase 3 randomized, controlled clinical trials was performed. UACR change from baseline after 24 weeks treatment with dapagliflozin 10 mg/d in 531 patients with type 2 diabetes and UACR ≥30 mg/g at baseline was determined. UACR response was defined as >30% reduction from baseline at 24 weeks, whereas UACR non-response was defined as ≤30% reduction at 24 weeks. A total of 288 (54%) patients were classified as responders and 243 (46%) as non-responders. At 24 weeks, the UACR-adjusted mean change from baseline was -71.2% and 25.9% in responders and non-responders, respectively. Baseline characteristics were similar between both groups. Changes in HbA1c and body weight were comparable across groups. Responders showed a numerically larger reduction in estimated glomerular filtration rate and systolic blood pressure versus non-responders. UACR reduction to dapagliflozin is an individual characteristic that cannot be predicted by baseline clinical features or changes in metabolic variables. Whether UACR response would improve long-term renal and cardiovascular outcomes remains to be determined.

Intinerário terapêutico de pessoas com DM2 que sofreram amputação: (des) encontros com os profissionais e o sistema de saúde / Therapeutic itinerary of people with DM2 who suffered amputation: (dis) meetings with professionals and the health system

Objetivo: analisar o itinerário terapêutico de usuários da APS que sofreram amputação de membro inferior por complicação da Diabetes Mellitus tipo 2, abordando aspectos relacionados aos profissionais de saúde e a organização do sistema de saúde em diferentes níveis de atenção. Método: Pesquisa qualitativa, realizada com seis usuários que sofreram amputação de membros inferiores derivados do DM2 de um serviço de Atenção Primária. A coleta de dados foi realizada mediante pesquisa nos prontuários e entrevista semi-estruturada, gravadas, transcritas e analisadas à luz da Análise de Conteúdo. Resultados: Emergiram duas categorias relacionadas ao itinerário da amputação e os des(encontros) com os profissionais da saúde e sistema de saúde. Considerações finais: Diante disso, os itinerários terapêuticos dos sujeitos demonstraram as fragilidades da Rede de Atenção á Saúde no cuidado do portador de DM. Foram muitos desencontros na busca por cuidado, situações traumáticas e falta de sensibilidade com sua condição de saúde. (AU)

Application of urinary proteomics as possible risk predictor of renal and cardiovascular complications in patients with type 2-diabetes and microalbuminuria.

BACKGROUND: Analyses of the urinary proteome have been proposed as a novel approach for early assessment of increased risk of renal- or cardiovascular disease. Here we investigate the potentials of various classifiers derived from urinary proteomics for prediction of renal and cardiovascular comorbidities in patients with type 2-diabetes. METHODS: The study was a post hoc analysis of the randomized controlled Steno-2 trial comparing intensified multifactorial intervention to conventional treatment of type 2-diabetes and microalbuminuria. 151 diabetic patients with persistent microalbuminuria were included in year 1995 and followed for up to 19 years. For renal outcomes, two classifiers (CKD273 and a novel, GFR-based classifier) and for cardiovascular outcomes, three classifiers (CAD238, ACSP and ACSP75) were applied. Renal endpoints were progression to macroalbuminuria, impaired renal function (GFR < 45 ml/min/1.73 m2) or progression to end stage renal disease (ESRD) or death. Cardiovascular endpoints were coronary artery disease and a composite endpoint of incident death of cardiovascular disease, myocardial infarction or revascularization, stroke, amputation or peripheral revascularization. RESULTS: CKD273 was not consistently associated with renal outcomes. The GFR-based classifier was associated with impaired renal function, but lost significance in extensively adjusted models. Both the ACSP75 and ACSP-scores, but not the CAD238-score were inversely associated (opposing the hypothesis) with cardiovascular endpoints. None of the classifiers improved prediction of any outcome on top of standard risk factors. CONCLUSIONS: Risk-scores based upon urinary proteomics did not improve prediction of renal and cardiovascular endpoints on top of standard risk factors such as age and GFR during long-term (19 years) follow up in patients with type 2-diabetes and microalbuminuria.

Urinary tubular biomarkers as predictors of kidney function decline, cardiovascular events and mortality in microalbuminuric type 2 diabetic patients.

AIMS: Urinary levels of kidney injury molecule 1 (u-KIM-1) and neutrophil gelatinase-associated lipocalin (u-NGAL) reflect proximal tubular pathophysiology and have been proposed as risk markers for development of complications in patients with type 2 diabetes (T2D). We clarify the predictive value of u-KIM-1 and u-NGAL for decline in eGFR, cardiovascular events (CVE) and all-cause mortality in patients with T2D and persistent microalbuminuria without clinical cardiovascular disease. METHODS: This is a prospective study that included 200 patients. u-KIM-1 and u-NGAL were measured at baseline and were available in 192 patients. Endpoints comprised: decline in eGFR > 30%, a composite of fatal and nonfatal CVE consisting of: cardiovascular mortality, myocardial infarction, stroke, ischemic heart disease and heart failure based on national hospital discharge registries, and all-cause mortality. Adjusted Cox models included traditional risk factors, including eGFR. Hazard ratios (HR) are provided per 1 standard deviation (SD) increment of log2-transformed values. Relative integrated discrimination improvement (rIDI) was calculated. RESULTS: During the 6.1 years' follow-up, higher u-KIM-1 was a predictor of eGFR decline (n = 29), CVE (n = 34) and all-cause mortality (n = 29) in adjusted models: HR (95% CI) 1.68 (1.04-2.71), p = 0.034; 2.26 (1.24-4.15), p = 0.008; and 1.52 (1.00-2.31), p = 0.049. u-KIM-1 contributed significantly to risk prediction for all-cause mortality evaluated by rIDI (63.1%, p = 0.001). u-NGAL was not a predictor of any of the outcomes after adjustment. CONCLUSIONS: In patients with T2D and persistent microalbuminuria, u-KIM-1, but not u-NGAL, was an independent risk factor for decline in eGFR, CVE and all-cause mortality, and contributed significant discrimination for all-cause mortality, beyond traditional risk factors.

Renal and Cardiovascular Risk According to Tertiles of Urinary Albumin-to-Creatinine Ratio: The Adolescent Type 1 Diabetes Cardio-Renal Intervention Trial (AdDIT).

OBJECTIVE: Baseline data from the Adolescent Type 1 Diabetes Cardio-Renal Intervention Trial (AdDIT) indicated that tertiles of urinary albumin-to-creatinine ratios (ACRs) in the normal range at age 10-16 years are associated with risk markers for diabetic nephropathy (DN) and cardiovascular disease (CVD). We aimed to determine whether the top ACR tertile remained associated with DN and CVD risk over the 2-4-year AdDIT study. RESEARCH DESIGN AND METHODS: One hundred fifty adolescents (mean age 14.1 years [SD 1.6]) with baseline ACR in the upper tertile (high-ACR group) recruited to the AdDIT trial, who remained untreated, and 396 (age 14.3 years [1.6]) with ACR in the middle and lower tertiles (low-ACR group), who completed the parallel AdDIT observational study, were evaluated prospectively with assessments of ACR and renal and CVD markers, combined with carotid intima-media thickness (cIMT) at baseline and end of study. RESULTS: After a median follow-up of 3.9 years, the cumulative incidence of microalbuminuria was 16.3% in the high-ACR versus 5.5% in the low-ACR group (log-rank P < 0.001). Cox models showed independent contributions of the high-ACR group (hazard ratio 4.29 [95% CI 2.08-8.85]) and HbA1c (1.37 [1.10-1.72]) to microalbuminuria risk. cIMT change from baseline was significantly greater in the high- versus low-ACR group (mean difference 0.010 mm [0.079], P = 0.006). Changes in estimated glomerular filtration rate, systolic blood pressure, and hs-CRP were also significantly greater in the high-ACR group (P < 0.05). CONCLUSIONS: ACR at the higher end of the normal range at the age of 10-16 years is associated with an increased risk of progression to microalbuminuria and future CVD risk, independently of HbA1c.

Elevated N-acetyl-ß-d-glucosaminidase, a urinary tubular damage marker, is a significant predictor of carotid artery atherosclerosis in type 1 diabetes, independent of albuminuria: A cross-sectional study.

AIMS: Recent evidence has shown that renal tubulointerstitial injuries play an important role in diabetic nephropathy. In this study, we evaluated the association between urinary N-acetyl-ß-d-glucosaminidase (uNAG), an early renal tubular damage marker, and carotid artery atherosclerosis in patients with type 1 diabetes (T1D). METHODS: This was a cross-sectional study of 88 patients with T1D. Demographic and laboratory data; urinary indices, including urinary NAG-to-creatinine ratio (uNCR), and albumin-to-creatinine ratio (uACR); and carotid ultrasonography were investigated. RESULTS: Eighty-eight subjects were divided into three groups based on uNCR tertiles. Subjects belonging to the highest tertile of uNCR had the highest average mean and maximum carotid intima-media thickness (IMT). An elevated uNCR was also significantly correlated with increased average mean and maximum carotid IMT, whereas an elevated uACR was not. Even after adjusting for confounding factors, uNCR continued to be a meaningful predictive marker for increased average mean and maximum IMT. Conversely, the uACR could not predict carotid IMT after adjustment for confounding factors. CONCLUSIONS: Elevated levels of uNAG are significantly associated with carotid artery atherosclerosis in patients with T1D independently of albuminuria, a marker of glomerular damage.

Arterial Stiffness Is More Associated with Albuminuria than Decreased Glomerular Filtration Rate in Patients with Type 2 Diabetes Mellitus: The REBOUND Study.

AIM: The aim of this study was to evaluate the association between arterial stiffness and albuminuria and glomerular filtration rate (GFR) in patients with type 2 diabetes mellitus. METHODS: This multicenter cohort study analyzed 2613 patients with type 2 diabetes. Brachial-ankle pulse wave velocity (baPWV) was used as a noninvasive marker of arterial stiffness. Additionally, the patients were categorized into four groups according to their albumin-to-creatinine ratio (ACR, normoalbuminuria versus albuminuria) and estimated GFR (eGFR, <60 mL/min/1.73 m2 versus ≥60 mL/min/1.73 m2). RESULTS: A univariate analysis revealed that maximal baPWV was significantly associated with both the ACR (r = 0.297, P < 0.001) and eGFR (r = -0.220, P < 0.001). A multivariate analysis adjusted for significant clinical variables and eGFR showed that baPWV remained significantly correlated with the ACR (r = 0.150, P < 0.001). Also, baPWV was correlated positively with the ACR in patients with an eGFR ≥ 60 mL/min/1.73 m2 (r = 0.146, P < 0.001). However, baPWV was not correlated with eGFR after adjustment for significant clinical variables. CONCLUSIONS: The present findings indicate that arterial stiffness is more associated with albuminuria than a decrease in GFR in patients with type 2 diabetes mellitus.

Association between plasma homocysteine levels and end-organ damage in newly diagnosed type 2 diabetes mellitus patients.

PURPOSE: The aim of the present study was to investigate the association between plasma homocysteine (Hcy) levels and carotid, cardiac, and renal end-organ damage in newly diagnosed type 2 diabetes mellitus (T2DM) patients. METHODS: Newly diagnosed normotensive T2DM patients (n = 390) were enrolled in this study. The patients were not taking any medications over the duration of the study. The left ventricular mass index (LVMI), carotid intima media thickness (CIMT), and creatinine levels and 24-h microalbuminuria were used to determine cardiac, carotid, and kidney end-organ diseases, respectively. RESULTS: Using univariate logistic regression analysis; age, 24-h microalbuminuria, fasting blood glucose, CIMT, creatinine level, and LVMI were found to be significantly associated with the Hcy level. When those six variables were included in a multivariate regression model, CIMT, LVMI, and creatinine were found to be significantly associated with the Hcy level. We determined that an Hcy level >12.5 µmol/L was predictive of high LVMI, with a sensitivity of 70.1% and a specificity of 68%. An Hcy level >13.5 µmol/L was predictive of high CIMT, with a sensitivity of 67.5% and a specificity of 63.1%. CONCLUSION: In this study, LVMI, CIMT, and creatinine level were positively correlated with the Hcy level. We believe that the Hcy level may be a useful predictor of end-organ damage, including cardiac, carotid, and renal diseases, in newly diagnosed T2DM patients.

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.

Evaluation of ultrasensitive CRP and microalbuminuria as cardiovascular risk markers in type 2 diabetic moroccan patients.

INTRODUCTION: Type 2 diabetes is a chronic disease whose prevalence is increasing exponentially. This condition is a risk factor for cardiovascular disease, the leading cause of death among diabetics. AIM: To study the correlation between hs CRP, microalbuminuria, diabetes monitoring parameters and the presence of vascular complications in a group of non-insulin dependent diabetic patients followed in endocrinology department of the Moulay Ismail Military Hospital in Meknes. METHODS: The study involved 250 patients with type 2 diabetes and 120 control subjects. Patients were subduvised on 2 groups: group I consisting of patients without diabetes vascular complications. Group II involved patients with at least one vascular complication. The parameters measured were age, sex, BMI, duration of diabetes and the presence of vascular complications. The studied biological parameters were hs CRP, microalbuminuria, HbA1c and lipid profile. RESULTS: Diabetic patients with complications had significantly higher levels of hs CRP and microalbuminuria compared with diabetic patients without complications and with controls (8.37 vs 5.94 vs 2.63; p <0.001 vs 62.10 34 56 vs 5.67; p <0.0001). The rate of hs CRP were significantly correlated with HA1c, total cholesterol, the LDL-C, index atherogenicity microalbuminuria and duration of diabetes for the two patient groups. A significant correlation between hs CRP and age was only found in Group I. CONCLUSION: CRP appears to be interested in the detection of vascular complications in diabetic type2.

Factors associated with the reduction of albumin excretion in diabetic hypertensive patients: differential effect of manidipine versus amlodipine.

AIMS: In AMANDHA trial, the addition of manidipine, but not amlodipine, in diabetic patients with uncontrolled hypertension, microalbuminuria and preserved renal function resulted in a large decrease of urinary albumin excretion (UAE) despite similar blood pressure (BP) reductions. Factors associated with the reduction of UAE were analyzed. METHODS: For this purpose, a multivariable analysis was performed. RESULTS: Although after 6 months of treatment, manidipine and amlodipine decreased BP to a similar extent, reductions of UAE were higher with manidipine. The assigned treatment, changes in mean BP, sympathetic tone and glycemic control were associated with changes in UAE. CONCLUSION: The assigned treatment, changes in mean BP, sympathetic tone and glycemic control were independently associated with changes in UAE. Compared with amlodipine, manidipine reduced UAE to a higher extent, independently of BP reduction.

Oxidative DNA damage is associated with inflammatory response, insulin resistance and microvascular complications in type 2 diabetes.

Urinary markers of nucleic acid oxidation may be useful biomarkers in diabetes. It has been demonstrated that T2DM patients have an increased level of oxidative DNA damage; however, it is unclear whether increased DNA damage may be related to a greater degree of inflammation and insulin resistance. Thus, the aim of this present study was to investigate the relation of the impact of oxidative DNA damage, assessed by urinary 8-OHdG, on the levels of inflammatory cytokines, as well as insulin resistance. In addition, we also investigated the diagnostic ability of urinary 8-OHdG in the identification of microvascular complications in T2DM.A case-control study, enrolling 22 healthy controls and 54 subjects with T2DM, was performed to evaluate the relation between oxidative DNA damage and interleukin-6 (IL-6), IL-1,tumor necrosis factor-alpha (TNF-α), IL-10, and Homeostasis Model Assessment (HOMA-IR) index. T2DM patients presented higher urinary 8-OHdG, IL-6, IL-1, TNF-α levels and HOMA-IR, and lower IL-10 levels than control subjects. Moreover, urinary 8-OHdG levels were significantly higher in the group T2DM with microvascular complications when compared to the without complications. The areas under the curve for urinary 8-OHdG and urinary albumin were, respectively, 0.836 (P<0.001) and 0.786 (P=0.002). Thus, urinary 8-OHdG has a slightly higher ability to discriminate microvascular complications in T2DM compared with urinary albumin. It was also demonstrated that T2DM patients with higher median of urinary 8-OHdG had significantly elevated levels of IL-6, TNF-α and HOMA-IR, and decreased IL-10 levels. Our findings showed that T2DM patients with higher urinary 8-OHdG levels showed a greater inflammatory degree and higher insulin resistance. It is possible to speculate that T2DM patients present a cascade of events as increasing metabolic abnormalities such as insulin resistance and inflammatory activation, as well as increased ROS generation factors that may contribute directly to greater oxidative DNA damage.

A New Proposal for the Target Value for Home BP in Type 2 Diabetes Patients: The J-HOP Study.

OBJECTIVE: The target levels of home-monitored blood pressure (BP) in patients with type 2 diabetes mellitus (T2DM) have not yet been established. We sought to examine the appropriate target home BP level in T2DM. METHODS: This is a subanalysis of the Japan Morning Surge-Home Blood Pressure (J-HOP) study. We enrolled 4,310 patients who had at least 1 cardiovascular risk factor, and clinic and home BP monitoring was performed. The urinary albumin-to-creatinine ratio (UACR) was measured as a marker of microvascular disease. Quadratic equations of the relationship between clinic/home systolic BP (SBP) and log-transformed UACR were used to determine the home BP value. Home BP levels corresponding to clinic SBP/diastolic BP (DBP) level using the UACR values were calculated separately by the presence/absence of diabetes. RESULTS: The mean age of the patients was 64.9±10.9 years; 47.0% were males. Of the 4,310 subjects enrolled, 1,057 (24.5%) had T2DM (the DM group) and 3,253 (75.5%) did not (non-DM group). The home BP levels equivalent to clinic BP 140/90 mm Hg were 135/84 and 135/83 mm Hg in the DM and non-DM groups, respectively. The home SBP levels equivalent to clinic SBP 130/80 mm Hg were 122/79 mm Hg in the non-DM group and 129/78 mm Hg in the DM group. CONCLUSIONS: Regardless of diabetic status, the home BP level that corresponds to the clinic SBP 140/90 mm Hg was 135/85 mm Hg. In patients with T2DM, the home SBP level equivalent to clinic SBP 130/80 mm Hg was 129/78 mm Hg with regard to the extent of microvascular disease.

Glycated peptides are associated with the variability of endothelial dysfunction in the cerebral vessels and the kidney in type 2 diabetes mellitus patients: a cross-sectional study.

BACKGROUND: Diabetic atherosclerosis and microangiopathy parallel diabetic nephropathy. The aim of our study was to evaluate the pattern of endothelial dysfunction in two vascular territories, the kidney and the brain, both affected by diabetic vasculopathic complications. The endothelial variability was evaluated in relation to advanced glycation end-products modified peptides. METHODS: Seventy patients with type 2 diabetes mellitus and 11 healthy subjects were assessed concerning urine albumin: creatinine ratio, plasma and urinary advanced glycation end-products, plasma asymmetric dimethyl-arginine, serum cystatin C, intima-media thickness in the common carotid arteries, the pulsatility index, the resistance index in the internal carotid arteries and the middle cerebral arteries, the cerebrovascular reactivity through the breath-holding test. RESULTS: The breath-holding index correlated with asymmetric dimethyl-arginine (R²=0.151; p<0.001), plasma advanced glycation end-products (R²=0.173; p<0.001), C-reactive protein (R²=0.587; p<0.001), duration of diabetes mellitus (R²=0.146; p=0.001), cystatin C (R²=0.220; p<0.001), estimated glomerular filtration rate (R²=0.237; p=0.001). Urine albumin: creatinine ratio correlated with urinary advanced glycation end-products (R²=0.257; p<0.001), but not with asymmetric dimethyl-arginine (R²=0.029; p=0.147). CONCLUSIONS: In type 2 diabetic patients endothelial dysfunction in the cerebral vessels appears to be dissociated from glomerular endothelial dysfunction in early diabetic nephropathy. Advanced glycation end-products could impact both the cerebral vessels and the glomerular endothelium.