Albumin Excretion In Patients Research Articles

Improvement in albumin excretion in patients with type 2 diabetes mellitus labelled as metformin-intolerant after rechallenge with extender-release metformin

Improvement in albumin excretion in patients with type 2 diabetes mellitus labelled as metformin-intolerant after rechallenge with extender-release metformin

DAPagliflozin for the attenuation of albuminuria in Patients with hEaRt failure and type 2 diabetes (DAPPER study): a multicentre, randomised, open-label, parallel-group, standard treatment-controlled trial

Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the urinary albumin-to-creatinine ratio (UACR) in patients with elevated levels of albuminuria in the presence or absence of heart failure (HF) or type 2 diabetes mellitus (T2D). However, these effects have not yet been reported in the presence of both HF and T2D. This lack of evidence prompted us to conduct a clinical trial on the effects of dapagliflozin on UACR in patients with HF and T2D. DAPPER is a multicentre, randomised, open-labeled, parallel-group, standard treatment-controlled trial that enrolled patients at 18 medical facilities in Japan. Eligible participants with both HF and T2D and aged between 20 and 85 years were randomly assigned to a dapagliflozin or control (anti-diabetic drugs other than SGLT 2 inhibitors) group with a 1:1 allocation. The primary outcome was changes in UACR from baseline after a two-year observation, and secondary endpoints were cardiovascular (CV) events and parameters related to HF. This trial was registered with the UMIN-CTR registry, UMIN000025102 and the Japan Registry of Clinical Trials, jRCTs051180135. Between 12 May 2017 and 31 March 2020, 294 patients were randomly assigned to the dapagliflozin group (n=146) or control group (n=148). The mean age of patients was 72.1 years and 29% were female. The mean glycated hemoglobin value was 6.9%, mean NT-proBNP was 429.1pg/mL, mean estimated GFR was 65.7mL/min/1.73m2, and median UACR was 25.0 (8.8-74.6) mg/g Cr in the dapagliflozin group and 25.6 (8.2-95.0) mg/g Cr in the control group. Of the 146 patients in the dapagliflozin group, 122 completed the study, and 107 (87.7%) were taking 5mg of dapagliflozin daily at the end of the observation period. The primary outcome did not significantly differ between the dapagliflozin and control groups. Among the secondary endpoints, the mean decrease in left ventricular end-diastolic dimensions as one of the echocardiographic parameters was larger in the dapagliflozin group than in the control group. The composite endpoint, defined as CV death or hospitalisation for CV events, hospitalisation for HF events, hospitalisation for all causes, and an additional change in prescriptions for heart failure in a two-year observation, was less frequent in the dapagliflozin group than in the control group. Although dapagliflozin at a dose of 5mg daily did not reduce urinary albumin excretion in patients with HF and T2D from that in the controls, our findings suggest that dapagliflozin decreased CV events and suppressed left ventricular remodeling. AstraZeneca KK, Ono Pharmaceutical Co., Ltd.

Relationship between plasma leucine-rich α-2-glycoprotein 1 and urinary albumin excretion in patients with type 2 diabetes.

To explore the relationship between plasma leucine-rich α-2-glycoprotein 1 (LRG1) level and the degree of urinary albumin excretion in patients with type 2 diabetes. We evaluated 332 patients with type 2 diabetes in a cross-sectional study. The plasma LRG1 level differed significantly according to the quartiles of urinary albumin excretion (Q1 [<7.7 mg/g], 17.1 μg/mL; Q2 [7.7-15.0 mg/g], 17.5 μg/mL; Q3 [15.1-61.4 mg/g], 18.6 μg/mL; Q4 [≥61.5 mg/g], 22.3 μg/mL; p for trend = 0.003) under adjustment with other covariates. A positive correlation was found between plasma LRG1 level and urinary albumin excretion (ρ = 0.256, p <0.001). According to a multivariate model, the association between LRG1 and urinary albumin excretion remained significant, under adjustment for confounding factors (β = 0.285, p <0.001). Plasma LRG1 level was independently associated with urinary albumin excretion in patients with type 2 diabetes. This study suggests that LRG1 may be associated with increased excretion of urinary albumin in the early stages of diabetic nephropathy.

Association between Diabetic Peripheral Neuropathy as Measured Using a Point-of-Care Sural Nerve Conduction Device and Urinary Albumin Excretion in Patients with Type 2 Diabetes.

It is not well known whether diabetic peripheral neuropathy diagnosed using a non-invasive point-of-care nerve conduction device called DPN-Check® is associated with diabetic nephropathy. Thus, we aimed to evaluate the association of diabetic peripheral neuropathy with urinary albumin excretion in patients with type 2 diabetes using DPN-Check®. This retrospective observational study included 323 Japanese patients with type 2 diabetes. The urinary albumin-to-creatinine ratio in a spot urine sample was defined as urinary albumin excretion. Multiple linear regression analysis was used to determine the association of DPN-Check®-determined diabetic peripheral neuropathy with urinary albumin excretion. Patients with DPN-Check®-determined diabetic peripheral neuropathy had significantly higher urinary albumin excretion than those without, while there was no difference in urinary albumin excretion between patients with and without diabetic peripheral neuropathy determined by simplified diagnostic criteria. In the multivariate model, the DPN-Check® determined that diabetic peripheral neuropathy was significantly associated with urinary albumin excretion even after adjustment for covariates (standardized β, 0.123; p = 0.012). Our study found a significant association between diabetic peripheral neuropathy diagnosed using DPN-Check® and urinary albumin excretion in patients with type 2 diabetes.

Prevalence and association of diabetic nephropathy in newly diagnosed Chinese patients with diabetes in the Hebei province: A single-center case-control study.

Diabetes is a chronic disease and has huge pressure on patients and the medical system, especially for patients with diabetic complications, for example, diabetic nephropathy. Diabetic nephropathy is a diabetic complication associated with damage to the kidney. To improve the quality of life of patients with diabetes, it is necessary to understand the factors that are associated with diabetic nephropathy. The objective of the study was to find the prevalence of diabetic nephropathy in newly diagnosed patients with diabetes and to develop the association between clinicopathological parameters and diabetic nephropathy. In a case-control study, demographics, anthropometric, and clinicopathological parameters of a total of 305 newly diagnosed patients with diabetes (the fasting blood glucose ≥ 7.0 mM/L and/or glycosylated hemoglobin ≥ 6.5 mM/L) in Hebei province were included in the analysis. If the urine albumin to creatinine ratio was ≥ 30 (microalbuminuria) then patients were considered diabetic nephropathy. Among enrolled patients, 206 (68%) were males and 99 (32%) were females and they were 46 to 71 years old. Demographic variables and health-related behaviors were the same among patients with diabetes either with nephropathy (case group, n = 135) or patients without nephropathy (control group, n = 170, P > .05 for all). The prevalence of diabetic nephropathy was 44%. Female to male ratio was 1:1.7 in the case group. Patients with diabetic nephropathy had higher body weight (P < .0001), waist circumference (P = .0006), and body mass index (P = .0002) than those of patients without nephropathy. Abnormal urinary globulin (P = .041, odd ratio (OR): 1.1231) was associated with diabetic nephropathy. Aspartate transaminase (P = .0651, OR: 0.8541), alkaline phosphatase (P = .0661, OR: 0.8122), hypertension (P = .0821, OR: 0.8214), and blood urea nitrogen (P = .0842, OR: 0.9411) were not significantly associated with diabetic neuropathy. However, they are near the statistical cutoff value. The prevalence of diabetic nephropathy in newly diagnosed diabetic patients of Hebei province is higher than those of the other provinces. Urinary globulin excretion had a weak association with the presence of nephropathy defined by urinary albumin excretion in patients with diabetes. The presence of other diabetic complications is also an essential parameter for diabetic nephropathy. Males are more susceptible to diabetic nephropathy than females if diabetic (Evidence Level: V; Technical Efficacy: Stage 3).

Impact of salt intake on urinary albumin excretion in patients with type 2 diabetic nephropathy: a retrospective cohort study based on a generalized additive model.

Diabetic kidney disease is an important and common cause of end-stage renal disease. Measurement of urinary albumin excretion (UAE) requires the diagnosis of the stage of diabetic nephropathy and the prognosis of renal function. We aimed to analyze the impact of lifestyle modification on UAE in patients with stage 2 and 3 type 2 diabetic nephropathy who received comprehensive medical care, using a generalized additive model (GAM), an explanatory machine learning model. In this retrospective observational study, we used changes in HbA1c, systolic blood pressure (SBP), and diastolic blood pressure (DBP) levels; body mass index (BMI); and daily salt intake as factors contributing to changes in UAE. In total, 269 patients with type 2 diabetic nephropathy were enrolled (stage 2, 217 patients; stage 3, 52 patients). The rankings that contributed to changes in UAE over 6 months by permutation importance were the changes in daily salt intake, HbA1c, SBP, DBP, and BMI. GAM, which predicts the change in UAE, showed that with increase in the changes in salt intake, SBP, and HbA1c, the delta UAE tended to increase. Salt intake was the most contributory factor for the changes in UAE, and daily salt intake was the best lifestyle factor to explain the changes in UAE. Strict control of salt intake may have beneficial effects on improving UAE in patients with stage 2 and 3 diabetic nephropathy.

Effect of dapagliflozin on urinary albumin excretion in patients with chronic kidney disease with and without type 2 diabetes: a prespecified analysis from the DAPA-CKD trial

Reductions in albuminuria are associated with a subsequent lower risk of kidney failure in patients with chronic kidney disease. The SGLT2 inhibitor dapagliflozin significantly reduced albuminuria in patients with type 2 diabetes and normal or near-normal kidney function. Whether this effect persists in patients with chronic kidney disease with and without type 2 diabetes is unknown. We assessed the effects of dapagliflozin on albuminuria in patients with chronic kidney disease with and without type 2 diabetes in the dapagliflozin and prevention of adverse outcomes in chronic kidney disease (DAPA-CKD) trial. DAPA-CKD was a multicentre, double-blind, placebo-controlled, randomised trial done at 386 sites in 21 countries. Patients were eligible for the trial if they had chronic kidney disease, defined as an estimated glomerular filtration rate (eGFR) between 25 mL/min per 1·73 m2 and 75 mL/min per 1·73 m2 and a urinary albumin-to-creatinine ratio (UACR) between 200 mg/g and 5000 mg/g (22·6 to 565·6 mg/mmol). Participants were randomly assigned to dapagliflozin 10 mg (AstraZeneca; Gothenburg, Sweden) once daily or matching placebo, in accordance with the sequestered, fixed randomisation schedule, using balanced blocks to ensure an approximate 1:1 ratio. Change in albuminuria was a pre-specified exploratory outcome of DAPA-CKD. Regression in UACR stage, defined as a transition from macroalbuminuria (≥300 mg/g) to microalbuminuria or normoalbuminuria (<300 mg/g), and progression in UACR stage, defined as a transition from less than 3000 mg/g to 3000 mg/g or greater, were additional discrete endpoints. The trial is registered with ClinicalTrials.gov, NCT03036150. Between Feb 2, 2017, and April 3, 2020, 4304 patients were recruited and randomly assigned to either dapagliflozin (n=2152) or placebo (n=2152). Median UACR was 949 mg/g (IQR 477 to 1885). Overall, compared with placebo, dapagliflozin reduced geometric mean UACR by 29·3% (95% CI -33·1 to -25·2; p<0·0001); relative to placebo, treatment with dapagliflozin resulted in a geometric mean percentage change of -35·1% (95% CI -39·4 to -30·6; p<0·0001) in patients with type 2 diabetes and -14·8% (-22·9 to -5·9; p=0·0016) in patients without type 2 diabetes over the follow-up visits (pinteraction<0·0001) Among 3860 patients with UACR of 300 mg/g or greater at baseline, dapagliflozin increased the likelihood of regression in UACR stage (hazard ratio 1·81, 95% CI 1·60 to 2·05). Among 3820 patients with UACR less than 3000 mg/g at baseline, dapagliflozin decreased the risk of progression in UACR stage (0·41, 0·32 to 0·52). Larger reductions in UACR at day 14 during dapagliflozin treatment were significantly associated with attenuated eGFR decline during subsequent follow-up (β per log unit UACR change -3·06, 95% CI -5·20 to -0·90; p=0·0056). In patients with chronic kidney disease with and without type 2 diabetes, dapagliflozin significantly reduced albuminuria, with a larger relative reduction in patients with type 2 diabetes. The similar effects of dapagliflozin on clinical outcomes in patients with or without type 2 diabetes, but different effects on UACR, suggest that part of the protective effect of dapagliflozin in patients with chronic kidney disease might be mediated through pathways unrelated to reduction in albuminuria. AstraZeneca.

Association of circulating soluble lectin-like oxidized low-density lipoprotein receptor-1 with inflammatory markers and urinary albumin excretion in patients with type 2 diabetes.

Objectives:The main purpose of the study was to study the association between circulating soluble lectin-like oxidized low-density lipoprotein receptor-1 levels and various markers, including inflammatory markers such as high-sensitivity C-reactive protein and fibrinogen, serum lipids, and renal function, in patients with poorly controlled type 2 diabetes.Methods:The subjects were 70 patients (men 45, women 25) who were hospitalized for treatment of poor glycemic control. Plasma soluble lectin-like oxidized low-density lipoprotein receptor-1 levels were assayed using a sandwich chemiluminescence enzyme immunoassay.Results:Circulating soluble lectin-like oxidized low-density lipoprotein receptor-1 was significantly positively correlated with lectin-like oxidized low-density lipoprotein-1 ligands containing apolipoprotein B, reflecting modified low-density lipoprotein, and with inflammatory markers such as high-sensitivity C-reactive protein and fibrinogen. In addition, there was a significant positive correlation between soluble lectin-like oxidized low-density lipoprotein receptor-1 and urinary albumin excretion.Conclusions:Soluble lectin-like oxidized low-density lipoprotein receptor-1 may serve as a marker reflecting the degrees of inflammation and albuminuria in patients with poorly controlled type 2 diabetes.

Relations Between Urinary Albumin Excretion and a Dietary Intake of Fruits in Patients With Type 2 Diabetes.

BackgroundIt was reported that microalbuminuria and a decline in renal function were associated with cardiovascular disease (CVD) mortality and renal events and prognostic serious complications. Dietary factors and nutrients affecting microalbuminuria in type 2 diabetes remain unclear, and accordingly we conducted a cross-sectional study on the possible relevance of dietary factors to urinary albumin excretion in patients with type 2 diabetes.MethodsForty-two patients with type 2 diabetes participated in this study, and these subjects were categorized into patients without microalbuminuria group with urine albumin-to-creatinine ratio (ACR) of less than 30 mg/g Cr (n = 29) and a microalbuminuria group with ACR of 30 - 299 mg/g Cr (n = 13). ACR levels were measured using spot urine samples. At the time of examination, body mass index (BMI) and systolic and diastolic blood pressures were measured and recorded. We performed sampling fasting-blood and spot urine and conducted a food frequency questionnaire based on food groups to examine dietary habits for the past 1 - 2 months.ResultsThere were no significant differences in sex, age, duration, BMI, blood pressures, biochemical data, and the median of daily intakes of energy and macronutrients between patients without microalbuminuria and microalbuminuria groups. In the intake of 17 food groups per day, fruits were significantly lower in the microalbuminuria group than in patients without microalbuminuria group (the median was 38 g vs. 120 g/day, P < 0.05), but intakes of other food groups were not significantly different between the two groups. Moreover, we examined a model of partial correlation between ACR to the intake of fruits, adjusted by age, sex, glycated hemoglobin and BMI. This partial correlation was insignificantly seen but close to a significant level (partial correlation coefficient: -0.270, P = 0.102).ConclusionsThese results suggest that the intake of fruits may be inversely associated with microalbuminuria in Japanese type 2 diabetic patients. It would be necessary to investigate the exact types and amounts of fruits to be consumed to address microalbuminuria.

Effect of high-dose mineralocorticoid receptor antagonist eplerenone on urinary albumin excretion in patients with type 2 diabetes and high cardiovascular risk: Data from the MIRAD trial

AimAs mineralocorticoid receptor antagonists (MRAs) may possess renoprotective effects in type 2 diabetes (T2D), it was decided to investigate the impact of high-dose MRA on prespecified secondary endpoints—namely, change in urinary albumin–creatinine ratio (UACR) and 24-h ambulatory blood pressure—in the MIRAD trial. MethodsThis was a double-blind clinical trial in which T2D patients at high risk of or with established cardiovascular disease (CVD) were randomized to either high-dose (100–200 mg) eplerenone or a dose-matched placebo as an add-on to background antihypertensive treatment for 26 weeks. Safety was evaluated by the incidence of hyperkalaemia and kidney-related adverse events. ResultsA total of 140 patients were enrolled (70 in each group). Baseline UACR was 17 mg/g (geometric mean; 95% CI: 13–22); this decreased by 34% in the eplerenone group compared with the placebo group at week 26 (95% CI: −51% to −12%; P = 0.005). There was no significant decrease in 24-h systolic blood pressure (SBP) due to treatment (−3 mmHg; 95% CI: −6 to 1; P = 0.150). However, the observed change in 24-h SBP correlated with the relative change in UACR in the eplerenone group (r = 0.568, P < 0.001). Mean baseline (± SD) estimated glomerular filtration rate (eGFR) was 85 (± 18.6) mL/min/1.73 m2, and 12 (± 9%) had an eGFR of 41–59 mL/min/1.73 m2. No significant differences in the incidence of mild hyperkalaemia (≥ 5.5 mmol/L; eplerenone vs placebo: 6 vs 2, respectively; P = 0.276) and no severe hyperkalaemia (≥ 6.0 mmol/L) were observed. ConclusionThe addition of high-dose eplerenone to T2D patients at high risk of CVD can markedly reduce UACR with an acceptable safety profile.

A Randomized, Double-Blind, Placebo-Controlled Clinical Trial of an Omega-3 Fatty Acid Supplement in Patients With Predialysis Chronic Kidney Disease

Omega-3 fatty acids may reduce albuminuria and cardiovascular risk factors in patients with chronic kidney disease (CKD). We aimed to assess the effects of omega-3 fatty acid supplementation on albuminuria, blood pressure, pulse wave velocity, and inflammatory markers in patients with CKD. Patients with CKD and a urine albumin excretion of at least 30mg/g creatinine were supplemented for 3months with 3,666mg/day of docosahexaenoic and eicosapentaenoic acids or a corn oil supplement. The study was double blind. At baseline, 6 weeks, and 12weeks, fasting blood and morning spot urine samples were obtained. Blood pressure, carotid intima media thickness, and pulse wave velocity were measured. The main outcome measure was a reduction of ≥20% in urine albumin. One hundred patients were randomized (50 received omega-3 fatty acids and 50 received corn oil). Four patients who received omega-3 fatty acids and 5 who received vegetable oil were lost to follow-up. In patients receiving omega-3 fatty acids, the omega-3 index increased from 3.08 (2.32-3.81) to 5.48 (3.045-7.04) percent. A 20% reduction in urine albumin excretion was observed in 13 participants of the control group and 19 participants of omega-3 group (Fisher's exact P=.274). However, the supplement had a significant and positive effect on pulse wave velocity and triglyceride level. An omega-3 fatty acid supplement of 3,666mg/day did not modify urine albumin excretion in patients with CKD but did improve pulse wave velocity and serum triglyceride levels.

Exenatide once weekly decreases urinary albumin excretion in patients with type 2 diabetes and elevated albuminuria: Pooled analysis of randomized active controlled clinical trials.

AimsTo examine the albuminuria‐lowering effect of exenatide once weekly (EQW) compared with active glucose‐lowering comparators in patients with type 2 diabetes and elevated urinary albumin‐to‐creatinine ratio (uACR).MethodsSix randomized double‐blind and open‐label phase III studies were pooled in a post hoc, exploratory analysis to evaluate the efficacy and safety of EQW versus non‐glucagon‐like peptide‐1 receptor agonist comparators in patients with type 2 diabetes and baseline uACR ≥30 mg/g. Treatment groups were EQW versus all comparators pooled. Efficacy outcomes were percent change from baseline to week 26/28 in uACR and absolute change in glycated haemoglobin (HbA1c), systolic blood pressure (SBP), body weight and estimated glomerular filtration rate (eGFR).ResultsBaseline characteristics were generally similar between the two treatment groups (EQW: N = 194, all comparators: N = 274). Relative to the comparator group, EQW changed albuminuria by −26.2% (95% confidence interval [CI] −39.5 to −10). Similar improvements were observed with EQW versus oral glucose‐lowering drugs (−29.6% [95% CI −47.6 to −5.3) or insulin (−23.8% [95% CI −41.8 to −0.2]). The effect of EQW on uACR was independent of baseline renin‐angiotensin system inhibitor usage. Adjusted mean decreases in HbA1c, SBP and body weight were more pronounced in the EQW versus the comparator group. Adjustment for changes in HbA1c, eGFR and SBP did not substantially affect the uACR‐lowering effect of EQW. When also adjusting for changes in body weight, the uACR‐lowering effect was reduced to (−13.0% [95% CI −29.9 to 7.8]).ConclusionExenatide once weekly reduced uACR in patients with type 2 diabetes and elevated albuminuria compared to commonly used glucose‐lowering drugs.

Association of urinary albumin excretion with periodontal parameters in patients with type 2 diabetes mellitus: a cross-sectional study.

Our previous pilot study using patients with type 2 diabetes mellitus in one medical clinic showed an association of urinary albumin excretion, a marker of generalized vascular dysfunction and kidney damage, with periodontitis. The purpose of this study was to confirm the association by increasing the number of patients and medical clinics. Participants were 2302 patients (59.9% males, aged 29-93years) with type 2 diabetes mellitus from 25 medical clinics. Their medical records and information about socioeconomic status and health behavior were collected. Periodontal status was assessed in a nearby dental office. Multiple linear regression analyses were conducted to examine the association of log-transformed urinary albumin-to-creatinine ratio with periodontal parameters after adjusting for sociodemographic status, general health conditions, and health behaviors. The analyses were performed in all subjects and subjects with normoalbuminuria only. Multiple linear regression analysis showed that mean probing pocket depth (beta: 0.062), percentage of sites with probing pocket depth of 4mm or deeper (beta: 0.068), percentage of mobile teeth (beta: 0.055), and severity of periodontitis (beta: 0.049) were significantly (p < 0.05) correlated with log-transformed urinary albumin-to-creatinine ratio after adjusting for possible confounders in all subjects. However, no significant associations between urinary albumin-to-creatinine ratio and periodontal parameters were observed in subjects with normoalbuminuria only. These results suggest that periodontitis is associated with urinary albumin excretion in patients with type 2 diabetes mellitus. Collaboration between medical and dental healthcare providers is needed for treatment of diabetes and periodontitis.

MON-304 Effect of Sodium-Glucose Co-transporter 2 Inhibitors in Patients with Diabetic Kidney Disease

The sodium-glucose co-transporter 2 inhibitor (SGLT2i) decreases HbA1c, body weight, blood pressure and urinary albumin excretion in patients with type 2 diabetes. The efficacy and safety of this drug have not been defined in patients with type 2 diabetes and moderate to severe renal impairment.

Significance of urinary albumin excretion inpatients with cast nephropathy .

Background: This study was performed to determine whether the urinary albumin excretion rate (%UAE) could distinguish myeloma cast nephropathy (MCN) without glomerular amyloid deposition from MCN with glomerular amyloid deposition. Materials and methods: We retrospectively reviewed clinicopathological data on 16 patients with MCN diagnosed by renal biopsy at Toranomon Hospital from 2004 to 2014. Results: A total of 10 patients had pure MCN without glomerular amyloid deposition (group 1), and 6 patients had MCN with glomerular amyloid deposition (group 2). In all 10 patients from group 1, the underlying disease was multiple myeloma (MM), while 4 patients had MM, and 2 patients had lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (LPL/WM) in group 2. Total protein did not show a significant difference between the two groups, but serum albumin was significantly higher in group 1 than group 2 (p = 0.0101). Serum-adjusted calcium did not show a significant difference between the groups, while serum creatinine (Cre) was significantly higher in group 1 than group 2 (p = 0.0343). Although urinary protein excretion did not differ significantly between the groups, the %UAE was significantly lower in group 1 than group 2 (p = 0.00198). In group 2, 3 of the 4 patients with MM died within 15 months of diagnosis, but the 2 patients with LPL/WM are alive after 32 months. In group 1, only 1 patient died (of unknown causes) within 15 months after diagnosis. Conclusion: In patients with MCN, %UAE may be a useful marker for the detection of coexistence of glomerular lesions, such as amyloidosis, which are associated with a poor outcome.

Myocardial flow reserve assessed by cardiac 82Rb positron emission tomography/computed tomography is associated with albumin excretion in patients with Type 1 diabetes.

AimsTo evaluate myocardial flow reserve (MFR) and coronary artery calcium (CAC) in persons with Type 1 diabetes with or without albuminuria and in non-diabetic controls. MFR reflects the function of large epicardial arteries and myocardial microcirculation. CAC represents structural aspects of atherosclerosis. In addition, we evaluated the association of MFR and CAC with retinopathy, another microvascular complication.Methods and resultsCross-sectional study in Type 1 diabetes, stratified by normoalbuminuria (NORMO; n = 30) and macroalbuminuria (MACRO; n = 30), and in non-diabetic controls (n = 30). MFR (pharmacological stress flow/rest flow) was evaluated by cardiac 82Rb positron emission tomography/computed tomography. MFR was similar in patients with NORMO and controls (3.1 ± 0.79 vs. 3.0 ± 0.79; P = 0.74). Patients with MACRO had lower (impaired) MFR when compared with NORMO (2.1 ± 0.92 vs. 3.1 ± 0.79; P < 0.0001). The CAC score [median (interquartile range)] was higher in NORMO when compared with controls [72 (22–247) vs. 0 (0–81), P = 0.03], and comparable between MACRO and NORMO. MFR was comparable in patients with diabetes and simplex or no retinopathy (n = 24 and n = 12, 2.8 ± 0.84 vs. 3.3 ± 0.77, P = 0.11), but lower in proliferative (n = 24) compared with simplex retinopathy (2.1 ± 0.97 vs. 2.8 ± 0.84, P = 0.02). The CAC score was comparable between groups of retinopathy.ConclusionMyocardial microvascular function was comparable in non-diabetic controls and patients with Type 1 diabetes and NORMO; but impaired in the presence of microvascular complications (MACRO and proliferative retinopathy). Coronary calcification was elevated in diabetes, however, not explained by albuminuria.

A3993 Myocardial flow reserve assessed by Cardiac 82Rb PET/CT is associated with albumin excretion in patients with type 1 diabetes

Objectives: To evaluate 1) myocardial flow reserve (MFR) and coronary artery calcium (CAC) in patients with type 1 diabetes (T1D) with or without albuminuria and in non-diabetic controls; 2) MFR and CAC in patients with T1D and retinopathy. MFR reflects the function of large epicardial arteries and myocardial microcirculation. CAC represents structural aspects of atherosclerosis. Methods: Cross-sectional study in T1D, stratified by normo- (n = 30) and macroalbuminuria (n = 30), and 30 controls. MFR and CAC was evaluated by cardiac 82Rb PET/CT. Results: MFR was similar in normoalbuminurics and controls (3.1 ± 0.8 vs 3.0 ± 0.79; p = 0.74). Macroalbuminurics had lower MFR compared to normoalbuminurics (2.1 ± 0.9 vs 3.1 ± 0.8; p < 0.0001). CAC score (median[IQR]) was higher in normoalbuminurics compared to controls (72[22–247] vs 0[0–81], p = 0.018), and comparable between macro- and normoalbuminurics. MFR was comparable in T1D with simplex retinopathy (n = 24) compared to no retinopathy (n = 12; p = 0.11), but lower in proliferative (n = 23) compared to simplex retinopathy (p = 0.02). CAC score was comparable between groups of retinopathy. Lower MFR was associated with higher CAC, UACR, age, 24-h SBP and lower eGFR. In multivariate regression lower MFR was associated with higher UACR and age, lower eGFR and smoking (R2 = 0.39). Higher CAC was associated with lower MFR, higher age and 24-h SBP (R2 = 0.34). Conclusion: Myocardial microvascular function was comparable in controls and patients with T1D and normoalbuminuria; but impaired in the presence of macroalbuminuria and/or proliferative retinopathy. Coronary calcification was also high, but not explained by albuminuria. This signifies that functional aspects of atherosclerosis correlate to albuminuria and retinopathy to larger extent than the structural.

Resveratrol reduces albuminuria in diabetic nephropathy: A randomized double-blind placebo-controlled clinical trial

AimAlbuminuria is the most important indicator of diabetic nephropathy (DN). Resveratrol, a natural compound found in grape skins and red wine, has antioxidant effects. This study aimed to evaluate the effects of resveratrol on DN. MethodsIn this randomized, double-blind, placebo-controlled clinical trial, 60 patients with type 2 diabetes and albuminuria were randomly assigned to receive either resveratrol (500mg/day) or placebo for 90 days. Losartan (12.5mg/day) was also administered to all participants. Primary outcomes were urinary albumin/creatinine ratio, estimated glomerular filtration rate (eGFR) and serum creatinine levels. Secondary outcomes were oxidative stress markers, and anthropometric and biochemical measures. ResultsMean urine albumin/creatinine ratio was significantly reduced in the resveratrol group vs placebo (−46.4mg/g, 95% CI: −64.5 to −28.3 vs 29.9mg/g, 95% CI: 4.9 to 54.9; P<0.001), whereas eGFR (1.7mL/min/1.73m2, 95% CI: −3.4 to 6.8 vs −4.0, 95% CI: −8.2 to 0.2; P=0.08) and serum creatinine (−0.3mg/dL, 95% CI: −0.1 to 0.1 vs 0.1mg/dL, 95% CI: −0.0 to 0.1; P=0.13) were unchanged. Serum antioxidant enzymes were significantly increased with resveratrol. After adjusting for confounding variables, the effect of resveratrol in reducing urinary albumin excretion was still significant (P<0.001). Regression analysis revealed that every 1-cm decrease in waist circumference and 1-μmol/L increase in nitric oxide (NO) was associated with 9.4mg/g and 4.0mg/g reductions, respectively, of urine albumin/creatinine ratio. ConclusionThis clinical trial has shown that resveratrol may be an effective adjunct to angiotensin receptor blockers (ARBs) for reducing urinary albumin excretion in patients with DN (ClinicalTrials.gov: NCT02704494).

Long-Term Effects of Ipragliflozin on Diabetic Nephropathy and Blood Pressure in Patients With Type 2 Diabetes: 104-Week Follow-up of an Open-Label Study.

BackgroundIn our previous study, we investigated the efficacy of ipragliflozin, a sodium-glucose cotransporter (SGLT) 2 inhibitor on diabetic nephropathy in patients with type 2 diabetes and demonstrated that ipragliflozin significantly improved diabetic nephropathy in addition to reducing HbA1c and body weight. Herein, we conducted post-trial monitoring to determine whether these lowering effects on blood glucose and body weight or the beneficial effects on diabetic nephropathy were maintained long-term (104 weeks) after starting ipragliflozin treatment.MethodsInitially, during a 24-week interventional trial period, a 50 mg dose of ipragliflozin was administered to 50 patients with type 2 diabetes without changing other treatments. During the post-trial monitoring period, these patients returned to hospital-based diabetes care according to their clinical needs. We continued monitoring their clinical data for 104 weeks in each hospital and analyzed the results on an intention-to-treat basis.ResultsThe improvements in glycemic control and body weight reduction provided by 24-week ipragliflozin administration were maintained for 104 weeks. Despite a transient decrease during the intervention period, the estimated glomerular filtration rate (eGFR) was restored to near the baseline level at 104 weeks. Notably, in patients with diabetic nephropathy, the median urinary albumin-to-creatinine ratio (UACR) was significantly decreased from 119.2 (98.9 - 201.8) at baseline to 36.9 (19.7 - 204.7) mg/gCr at 104 weeks. In addition, eGFR was stable for 104 weeks, showing no decrease. In contrast, a significant positive correlation between UACR and blood pressure observed at 24 weeks disappeared after discontinuation of the intervention therapy.ConclusionsThe well-controlled HbA1c and body weight reductions were maintained for 104 weeks of post-trial follow-up. Moreover, ipragliflozin significantly reduced urinary albumin excretion in patients with diabetic nephropathy without decreasing eGFR.

Relationships between the arterial velocity pulse index as a novel marker of atherosclerosis and biomarkers of cardiac or renal condition in patients with type 2 diabetes mellitus.

The arterial velocity pulse index (AVI) has been explored as a novel marker of atherosclerosis using pulse wave analysis in the clinical setting. The aim of this study was to clarify the relationships between the AVI and biomarkers of cardiac or renal condition in patients with type 2 diabetes mellitus. In total, 301 outpatients with type 2 diabetes mellitus (116 males and 185 females; mean age ±standard deviation: 63±12years) without a history of cardiovascular events were enrolled in this study. The AVI and biomarkers of cardiac or renal condition were measured using a commercial device, and the relationships between the AVI and the biomarkers were examined. The AVI was significantly associated with biomarkers of cardiac condition such as the blood levels of brain natriuretic peptide (r=0.29, P<0.001) and high-sensitivity cardiac troponin T (hs-cTnT) (r=0.48, P<0.001). The AVI was also significantly associated with biomarkers of renal condition such as the estimated glomerular filtration rate (r=-0.22, P<0.001) and urinary albumin excretion (r=0.42, P<0.001). Multiple regression analysis revealed that hs-cTnT and urinary albumin excretion were independent variables that were correlated with the AVI when it was used as a subordinate factor. The results of this study indicate that the AVI is significantly associated with hs-cTnT and urinary albumin excretion in patients with type 2 diabetes mellitus.