Maximum morning home systolic blood pressure is an indicator of the development of diabetic nephropathy: The KAMOGAWA-HBP study.
ABSTRACT: AIMS/INTRODUCTION:The maximum value of home systolic blood pressure is correlated with damage to target organs, including diabetic nephropathy. However, the precise relationship between the development of diabetic nephropathy and maximum home systolic blood pressure has not been elucidated. MATERIALS AND METHODS:In this prospective 2-year cohort subanalysis of the KAMOGAWA-HBP study, the patient population was 477 Japanese patients with normoalbuminuria. We investigated the effects of mean and maximum home blood pressure on the development of diabetic nephropathy, which we defined as a urinary albumin excretion value ≥30 mg/g creatinine. Among the 477 patients, 67 developed diabetic nephropathy. RESULTS:In our multivariate logistic regression analyses, the maximum morning home systolic blood pressure was significantly positively associated with the development of diabetic nephropathy after adjusting for patient sex and age, smoking status, the diabetes mellitus duration, body mass index, creatinine, total cholesterol, hemoglobin A1c, and antihypertensive medication use (odds ratio 1.21, 95% confidence interval 1.03-1.42, P = 0.021). CONCLUSIONS:Maximum home blood pressure can be identified at a glance, and its measurement would thus be helpful to healthcare providers who treat patients with diabetes and normoalbuminuria.
Project description:OBJECTIVE: To describe pregnancy outcome in type 1 diabetic women with normoalbuminuria, microalbuminuria, or diabetic nephropathy after implementation of an intensified antihypertensive therapeutic strategy. RESEARCH DESIGN AND METHODS: Prospective study of 117 pregnant women with type 1 diabetes. Antihypertensive therapy, mainly methyldopa, was given to obtain blood pressure <135/85 mmHg and urinary albumin excretion <300 mg/24 h. Blood pressure and A1C were recorded during pregnancy. The pregnancy outcome was compared with recently published studies of pregnant women with microalbuminuria or diabetic nephropathy. RESULTS: Antihypertensive therapy was given in 14 of 100 women with normoalbuminuria, 5 of 10 women with microalbuminuria, and all 7 women with diabetic nephropathy. Mean systolic blood pressure during pregnancy was 120 mmHg (range 101-147), 122 mmHg (116-135), and 135 mmHg (111-145) in women with normoalbuminuria, microalbuminuria, and diabetic nephropathy, respectively (P = 0.0095). No differences in mean diastolic blood pressure or A1C were detected between the groups. No women with microalbuminuria developed preeclampsia. The frequency of preterm delivery was 20% in women with normoalbuminuria and microalbuminuria in contrast to 71% in women with diabetic nephropathy (P < 0.01) where the median gestational age was 258 days (220-260). Compared with previous studies using less stringent antihypertensive therapeutic strategy and less strict metabolic control, gestational age was longer and birth weight was larger in our study. CONCLUSIONS: With intensified antihypertensive therapy and strict metabolic control, comparable pregnancy outcome was seen in type 1 diabetic women with microalbuminuria and normoalbuminuria. Although less severe than in previous studies, diabetic nephropathy was associated with more adverse pregnancy outcome.
Project description:<h4>Background</h4>A previous 2-year cohort study has shown that isolated high home systolic blood pressure (IH-HSBP) may increase the risk of diabetic nephropathy, using normal HBP as a reference. However, this association has not been previously assessed in the medium to long term.<h4>Methods</h4>This prospective 5-year cohort study of 424 patients, with normal or mildly increased albuminuria, investigated the effect of IH-HSBP on the risk of diabetic nephropathy in patients with type 2 diabetes mellitus. Diabetic nephropathy was defined as an advancement from normal or mildly increased albuminuira to moderate or severely increased albuminuria.<h4>Results</h4>Among 424 patients, 75 developed diabetic nephropathy during the study period. The adjusted odds ratio for developing diabetic nephropathy given IH-HSBP was 2.39 (95% confidence interval, 1.15-4.96, <i>p</i> = 0.02). The odds ratio for developing nephropathy in patients with IH-HSBP younger than 65 years was higher than that in patients with IH-HSBP older than 65 years.<h4>Conclusion</h4>IH-HSBP was associated with an increased risk of diabetic nephropathy among type 2 diabetes mellitus patients with normal or mildly increased albuminuria in the medium to long term. The results support and strengthen previous reports. These findings suggest that IH-HSBP might be a useful marker in disease prognostication.
Project description:Pharmacological blockade of the N- and L-type calcium channel lessens renal injury in kidney disease patients. The significance of specific blockade of ?1 subunit of N-type calcium channel, Cav2.2, in diabetic nephropathy, however, remains to be clarified. To examine functional roles, we mated Cav2.2(-/-) mice with db/db (diabetic) mice on the C57BLKS background. Cav2.2 was localized in glomeruli including podocytes and in distal tubular cells. Diabetic Cav2.2(-/-) mice significantly reduced urinary albumin excretion, glomerular hyperfiltration, blood glucose levels, histological deterioration and systolic blood pressure (SBP) with decreased urinary catecholamine compared to diabetic Cav2.2(+/+) mice. Interestingly, diabetic heterozygous Cav2.2(+/-) mice also decreased albuminuria, although they exhibited comparable systolic blood pressure, sympathetic nerve activity and creatinine clearance to diabetic Cav2.2(+/+) mice. Consistently, diabetic mice with cilnidipine, an N-/L-type calcium channel blocker, showed a reduction in albuminuria and improvement of glomerular changes compared to diabetic mice with nitrendipine. In cultured podocytes, depolarization-dependent calcium responses were decreased by ?-conotoxin, a Cav2.2-specific inhibitor. Furthermore, reduction of nephrin by transforming growth factor-? (TGF-?) in podocytes was abolished with ?-conotoxin, cilnidipine or mitogen-activated protein kinase kinase inhibitor. In conclusion, Cav2.2 inhibition exerts renoprotective effects against the progression of diabetic nephropathy, partly by protecting podocytes.
Project description:Purpose:The purpose of this study was to identify diabetic nephropathy risk factors in type 2 diabetes mellitus obese people based on community type 2 diabetes mellitus patients. Patients and Methods:In the community in Shanghai, we conduct a questionnaire, physical examination, and biochemical examination. The 406 patients included in the analysis were divided into two groups based on whether or not they had diabetic nephropathy. The influencing factors of type 2 diabetes mellitus obese patients were screened by the least absolute shrinkage and selection operator method, and then the influencing factors detected by the least absolute shrinkage and selection operator method were included in the binary logistic regression analysis, and the risk factors for diabetic nephropathy in obese people with type 2 diabetes mellitus were obtained. Finally, the nomogram and forest plot are used to visualize the binary logistic regression results, and the calibration plot and receiver-operating characteristic curve are used to verify the result. Results:The results showed that family history of diabetes (OR= 2.091, P= 0.002), disease course (OR=1.050, P= 0.007). hypertension (OR=1.768, P=0.042), hyperuricemia (OR=2.263, P=0.003), systolic blood pressure (OR=1.027, P<0.001), and glycosylated haemoglobin A1c (OR=1.358, P<0.001) were risk factors for diabetic nephropathy. Conclusion:For obese patients with type 2 diabetes mellitus, they should pay attention to family history of diabetes, disease course and hyperuricemia. Hypertension should be concerned and strictly controlled. Systolic blood pressure and glycosylated haemoglobin A1c will help prolong the survival of diabetic nephropathy patients.
Project description:This cross-sectional multicenter study was designed to evaluate the threshold value of home pulse pressure (PP) and home systolic blood pressure (SBP) predicting the arterial stiffness in 876 patients with type 2 diabetes. We measured the area under the receiver-operating characteristic curve (AUC) and estimated the ability of home PP to identify arterial stiffness using Youden-Index defined cut-off point. The arterial stiffness was measured using the brachial-ankle pulse wave velocity (baPWV). AUC for arterial stiffness in morning PP was significantly greater than that in morning SBP (P < .001). AUC for arterial stiffness in evening PP was also significantly greater than that in evening SBP (P < .001). The optimal cut-off points for morning PP and evening PP, which predicted arterial stiffness, were 54.6 and 56.9 mm Hg, respectively. Our findings indicate that we should pay more attention to increased home PP in patients with type 2 diabetes.
Project description:<h4>Aims/hypothesis</h4>The aim of the study was to determine the transition rate and factors associated with the progression of normo- and low microalbuminuria to diabetic nephropathy (overt proteinuria).<h4>Methods</h4>For 8 years we prospectively observed 1,558 Japanese patients with type 2 diabetes mellitus whose basal urinary albumin:creatinine ratio (UACR) had been measured as <17.0 mg/mmol at entry. The incidence of nephropathy (UACR >33.9 mg/mmol) was determined by measuring UACR twice a year.<h4>Results</h4>Progression to nephropathy occurred in 74 patients. The annual transition rate was 0.67%, and was substantially higher for the low-microalbuminuric group than for the normoalbuminuric group (1.85% and 0.23%, respectively; hazard ratio for the low-microalbuminuric group 8.45, p < 0.01). The hazard ratio for an HbA(1c) of 7-9% or ≥9% was 2.72 (p < 0.01) or 5.81 (p < 0.01) relative to HbA(1c) <7.0%, respectively. In comparison with individuals with a systolic blood pressure (SBP) of <120 mmHg, the hazard ratios for patients with an SBP of 120-140 mmHg or ≥140 mmHg were 2.31 (p = 0.06) and 3.54 (p < 0.01), respectively. Smoking also affected progression to proteinuria (hazard ratio 1.99, p < 0.01). In contrast, 30.3% of the low-microalbuminuric group returned to normoalbuminuria (i.e. were in remission).<h4>Conclusions/interpretation</h4>These results suggest that if patients with type 2 diabetes mellitus are receiving treatment from diabetologists for hyperglycaemia and hypertension when they are in the early stages of nephropathy (i.e. normo- or low microalbuminuria), their rate of transition to proteinuria is considerably lowered, and that differentiating patients with low microalbuminuria from those with high microalbuminuria might be clinically useful.<h4>Trial registration</h4>UMIN Clinical Trials Registry C000000222.
Project description:BACKGROUND:The Y-AIDA study was designed to investigate the renal- and home blood pressure (BP)-modulating effects of add-on dapagliflozin treatment in Japanese individuals with type 2 diabetes mellitus (T2DM) and albuminuria. METHODS:We conducted a prospective, multicenter, single-arm study. Eighty-six patients with T2DM, HbA1c 7.0-10.0%, estimated glomerular filtration rate (eGFR)???45 mL/min/1.73 m2, and urine albumin-to-creatinine ratio (UACR)???30 mg/g creatinine (gCr) were enrolled, and 85 of these patients were administered add-on dapagliflozin for 24 weeks. The primary and key secondary endpoints were change from baseline in the natural logarithm of UACR over 24 weeks and change in home BP profile at week 24. RESULTS:Baseline median UACR was 181.5 mg/gCr (interquartile range 47.85, 638.0). Baseline morning, evening, and nocturnal home systolic/diastolic BP was 137.6/82.7 mmHg, 136.1/79.3 mmHg, and 125.4/74.1 mmHg, respectively. After 24 weeks, the logarithm of UACR decreased by 0.37?±?0.73 (P?<?0.001). In addition, changes in morning, evening, and nocturnal home BP from baseline were as follows: morning systolic/diastolic BP -?8.32?±?11.42/-?4.18?±?5.91 mmHg (both P?<?0.001), evening systolic/diastolic BP -?9.57?±?12.08/-?4.48?±?6.45 mmHg (both P?<?0.001), and nocturnal systolic/diastolic BP -?2.38?±?7.82/-?1.17?±?5.39 mmHg (P?=?0.0079 for systolic BP, P?=?0.0415 for diastolic BP). Furthermore, the reduction in UACR after 24 weeks significantly correlated with an improvement in home BP profile, but not with changes in other variables, including office BP. Multivariate linear regression analysis also revealed that the change in morning home systolic BP was a significant contributor to the change in log-UACR. CONCLUSIONS:In Japanese patients with T2DM and diabetic nephropathy, dapagliflozin significantly improved albuminuria levels and the home BP profile. Improved morning home systolic BP was associated with albuminuria reduction. Trial registration The study is registered at the UMIN Clinical Trials Registry (UMIN000018930; http://www.umin.ac.jp/ctr/index-j.htm ). The study was conducted from July 1, 2015 to August 1, 2018.
Project description:<h4>Aims/introduction</h4>Postprandial hypotension (PPH) refers to a decrease in systolic blood pressure by ≥20 or to <90 mmHg from baseline ≥100 mmHg within 2 h of a meal. Previous studies have reported an association between diabetes and PPH; however, the characteristics of PPH in patients with diabetes remain unclear.<h4>Materials and methods</h4>We recruited patients with diabetes who regularly attended the diabetes outpatient clinic. Participants were instructed to carry out three sets of blood pressure measurements at six time points: just before and right after, and 30, 60, 90 and 120 min after their main meal of the day. Data on PPH symptoms were collected during an interview. To investigate the relationships between explanatory variables, PPH and associated symptoms, we carried out multiple logistic regression analyses.<h4>Results</h4>We analyzed data from 300 participants. There were 150 (50.0%) participants with PPH. Systolic blood pressure before a meal was significantly associated with PPH (odds ratio [OR] 1.56, 95% confidence interval [CI] 1.30-1.86, P < 0.001), after adjusting for covariates. Furthermore, age (OR 1.08, 95% CI 1.01-1.16, P = 0.027), hemoglobin A1c level (OR 2.39, 95% CI 1.01-5.64, P = 0.030) and coefficients of variation of R-R intervals (OR 0.79, 95% CI 0.65-0.97, P = 0.032) were significantly associated with asymptomatic PPH.<h4>Conclusions</h4>Half of the present study outpatients with diabetes had PPH. High systolic blood pressure before a meal was significantly associated with the risk of PPH. Older adults and patients with higher levels of hemoglobin A1c or an autonomic dysfunction might have difficulties recognizing symptoms of PPH.
Project description:BACKGROUND:Non-invasive measurements of 24 hour ambulatory central aortic systolic pressure (24 h-CASP) and central pulse pressure (24 h-CPP) are now feasible. We evaluate the relationship between 24 h central blood pressure and diabetes-related complications in patients with type 1 diabetes. METHODS:The study was cross-sectional, including 715 subjects: 86 controls (C), 69 patients with short diabetes duration (< 10 years), normoalbuminuria (< 30 mg/24 h) without receiving antihypertensive treatment (SN), 211 with longstanding diabetes (? 10 years) and normoalbuminuria (LN), 163 with microalbuminuria (30-299 mg/24 h) (Mi) and 186 with macroalbuminuria (> 300 mg/24 h) (Ma).24 h-CASP and 24 h-CPP was measured using a tonometric wrist-watch-like device (BPro, HealthStats, Singapore) and derived using N-point moving average. RESULTS:In C, SN, LN, Mi and Ma mean ± SD 24 h-CASP was: 114 ± 17, 115 ± 13, 121 ± 13, 119 ± 16 and 121 ± 13 mmHg (p < 0.001); and 24 h-CPP: 38 ± 8, 38 ± 7, 44 ± 10, 46 ± 11 and 46 ± 11 mmHg, (p < 0.001).Following rigorous adjustment (24 h mean arterial pressure and conventional risk factors), 24 h-CASP and 24 h-CPP increased with diabetes, albuminuria degree, previous cardiovascular disease (CVD), retinopathy and autonomic dysfunction (p ? 0.031).Odds ratios per 1 standard deviation increase in 24 h-CASP, 24 h-CPP and 24 h systolic blood pressure (24 h-SBP) were for CVD: 3.19 (1.68-6.05), 1.43 (1.01-2.02) and 2.39 (1.32-4.33), retinopathy: 4.41 (2.03-9.57), 1.77 (1.17-2.68) and 3.72 (1.85-7.47) and autonomic dysfunction: 3.25 (1.65-6.41), 1.64 (1.12-2.39) and 2.89 (1.54-5.42). CONCLUSIONS:24 h-CASP and 24 h-CPP was higher in patients vs. controls and increased with diabetic complications independently of covariates. Furthermore, 24 h-CASP was stronger associated to complications than 24 h-SBP.The prognostic significance of 24 h-CASP and 24 h-CPP needs to be determined in follow-up studies. TRIAL REGISTRATION:ClinicalTrials.gov ID NCT01171248.
Project description:Green tea (GT), through its antioxidant properties, may be useful to treat or prevent human diseases. Because several lines of evidence suggest that oxidative stress contributes to the pathogenesis of diabetic nephropathy, we tested the hypothesis that GT prevents diabetes and hypertension-related renal oxidative stress, attenuating renal injury. Spontaneously hypertensive rats (SHR) with streptozotocin-induced diabetes and nondiabetic SHR were treated daily with tap water or freshly prepared GT (13.3 g/L). After 12 wk, the systolic blood pressure did not differ between treated and untreated nondiabetic or diabetic rats. However, body weight was less (P < 0.05) and glycemia was greater in diabetic SHR rats than in nondiabetic rats. Renal oxidative stress variables such as 8-hydroxy-2'-deoxyguanosine (8-OHdG) and nitrotyrosine expression, NADPH oxidase-dependent superoxide generation, and the expression of renal cortex Nox4 were greater (P < 0.05) in diabetic rats that received water (DW) than in nondiabetic rats that received water (CW). The 8-OHdG and NADPH oxidase-dependent superoxide generation were significantly less in rats treated with GT. Nitrotyrosine and Nox4 expression were significantly less in diabetic rats that received GT (DGT) than in DW. Likewise, the indices of renal injury, albuminuria, and renal expression of collagen IV were significantly greater in DW than in CW. These differences were significantly less in DGT than in DW. GT reestablished the redox state and reduced the indicators of nephropathy without altering glycemia and blood pressure levels in diabetic SHR. These findings suggest that the consumption of GT may ameliorate nephropathy in diabetic hypertensive patients.