The accelerated formation of advanced glycation end products (AGEs) and the overexpression of transforming growth factor beta (TGF-␤ ) have both been implicated in the pathogenesis of diabetic microvascular and macrovascular complications. Previous studies in our laboratory have demonstrated that the vascular changes in diabetes include hypertrophy of the mesenteric vasculature. To examine the role of AGEs in this process, streptozotocin-induced diabetic rats and control animals were randomized to receive aminoguanidine, an inhibitor of AGE formation, or no treatment. Animals were studied at 7 d, 3 wk, and 8 mo after induction of diabetes. When compared with control animals, diabetes was associated with an increase in mesenteric vascular weight and an increase in media wall/lumen area. By Northern analysis, TGF-␤ 1 gene expression was increased 100-150% ( P Ͻ 0.01) and ␣ 1 (IV) collagen gene expression was similarly elevated to 30-110% compared to controls ( P Ͻ 0.05). AGEs and extracellular matrix were present in abundance in diabetic but not in control vessels. Treatment of diabetic rats with aminoguanidine resulted in significant amelioration of the described pathological changes including overexpression of TGF-␤ 1 and ␣ 1 (IV) collagen. These data implicate the formation of AGEs in TGF-␤ overexpression and tissue changes which accompany the diabetic state. ( J.

BackgroundSome previous observations suggest that insulin resistance and glucose metabolism disturbances are frequent complications of chronic kidney disease. However, there are no conclusive studies on other indices of the effectiveness of insulin action in end-stage renal disease (ESRD) patients, including chronically hemodialysed (HD) ones.Material/MethodsThe groups comprised 33 non-diabetic ESRD hemodialysed patients and 33 healthy controls matched for age, sex, and body mass index (BMI). In both groups, HOMA-%B, HOMA-%S, HOMA-IR indices, and DI were calculated using HOMA1 and HOMA2 as measures of insulin resistance. The indices were also assessed in subgroups divided according to BMI.ResultsMean fasting plasma glucose concentrations were lower in ESRD patients than in healthy persons (82.4±10.4 vs. 93.9±11.6, p=0.001). Fasting serum insulin concentrations were similar in both groups (median 6.8 vs. 6.0 mU/l, p=0.698). HOMA1-%B values were higher in ESRD patients than controls (median 137.1 vs. 81.6, p=0.002). HOMA1-%S (median 75.6 vs. 71.5) and HOMA1-IR (median 1.3 vs. 1.4) values were not significantly different (p=0.264 and p=0.189, respectively). DI1 levels were higher for HD patients than for healthy subjects (median 1.16 vs. 0.53, p<0.001). In subgroup analysis, all statistically significant differences were restricted mainly to persons with BMI <25 kg/m2. Similar results as for the HOMA1 model were obtained for HOMA2.Conclusions1. HOMA beta-cell function is strongly correlated with HOMA insulin resistance in HD patients. 2. In non-diabetic ESRD hemodialysed patients, the HOMA indices and DI may be useful and important models in interpretation of glucose metabolism disturbances.

The case we describe concerns a rapid progression of heart failure (HF) in a patient with hypertension crises (HC), haemodialysed (HD) with the use of a high-output arteriovenous fistula (AVF). The 48-year-old male with a body mass index of 19.27 kg/m 2 , renal insufficiency due to glomerulonephritis, treated with HD for two years (3 × 4.0 h/week), and with uncontrolled hypertension was admitted to the Military Institute of Medicine. On examination, reduced exercise tolerance, paroxysmal nocturnal dyspnoea and blood pressure (BP) 190/90 mm Hg were found. Laboratory tests revealed NT-pro B-type natriuretic peptide 302,009.0 pg/mL (n < 300.0). Echocardiography (ECHO) showed left ventricular (LV) hypertrophy (LV mass index [LVMI] 345.81 g/m 2 ), enlarged LV diastolic diameter [LVDD] 7.15 cm), with slightly decreased ejection fraction (EF 49%), Doppler signs of elevated cardiac output (CO 15.05 L/min; cardiac index (CI) 8.91 L/min/m 2 ), and pseudonormalised pattern of mitral inflow with elevated LV diastolic pressure (E/E' 31). In ultrasonographic examination of left shoulder AVF, an aneurysmal expansion of the lumen from 5.5 mm to 35 mm (Fig. 1), and significantly increased flow up to 2,532 mL/min (Fig. 2) were detected. Cardiopulmonary recirculation rate (CPR) was 0.17. Computed tomography excluded renal artery stenosis. In polysomnography, heavy central apnoea with an apnoea/hypopnoea index of 35.4/h was found. In 48-h ambulatory BP monitoring (ABPM), BP was 162/95 mm Hg. Treatment of sleep apnoea was implemented by a continuous positive airway pressure device, but this did not improve BP control. Upon discharge from hospital, the patient was overtreated with eight hypotensive drugs. After a month, HC occurred (BP 220/120 mm Hg) associated with acute coronary syndrome without ST-segment elevation. Coronarography found non-obstructive atherosclerotic plaques. Because of the suspicion of hyperkinetic state related to a lack of BP control, AVF was narrowed by implanting a polytetrafluorethylene graft of 4 mm diameter (Fig. 3). Despite AVF flow being reduced to 1,400 mL/min, after two months another HC (BP 220/125 mm Hg) with pulmonary oedema was presented. The next HC took place three months later. Although ECHO showed features of LV hypertrophy regression (LVMI 335.62 g/m 2 ), and significant decreases of CO (8.16 L/min) and CI (4.86 L/min/m 2 ), a decrease of EF (40%) and an LV dilatation enlargement (LVDD 7.7 cm) were also observed. AVF flow increased up to 1,750 mL/min and significant CPR 0.21 was indicated. In 24-h ABPM, BP was 173/105 mm Hg. The hypotensive treatment used has been confirmed by experts and seems to be optimal and safe for the cardiovascular system. Probably, AVF banding was performed too late, and progression of HF and lack of BP control improvement were observed. In hyperkinetic AVF, blood flow exceeds 2,000 mL/min and CPR is over 0.2-0.3. Currently, in cases of difficulties in surgical AVF creation and the necessity of haemodialysotherapy termination as a result of a lack of vascular access, ...

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We applied a recently reported method of decomposition of laser Doppler power density spectra for in vivo monitoring of speed distributions of red blood cells (RBCs) in the microvascular network. The spectrum decomposition technique allows us to derive the distribution of RBC speed (in absolute units (mm s(-1))) versus RBC concentration (in arbitrary units). We carried out postocclusive reactive hyperaemia (PORH) test in 15 healthy volunteers and 21 diabetic patients in which the duration of type 1 diabetes was longer than 10 years. Measurements were carried out simultaneously with the use of a typical laser Doppler commercial instrument and speed resolved laser Doppler instrument utilizing the new technique based on decomposition of the laser Doppler spectra. We show that for the classical laser Doppler instrument, none of the PORH parameters revealed a statistical significance of difference between the groups analyzed. In contrast, the RBC speed distributions obtained from laser Doppler spectra during rest in the control group and type 1 diabetes are statistically significant. This result suggests that speed distribution measurements in the rest state (without any kind of stimulation test) allows for the assessment of microcirculation disorders. Measurements carried out in healthy subjects show that the first moment of speed distributions (mean speed of the distributions) is 2.32 ± 0.54 mm s(-1) and 2.57 ± 0.41 mm s(-1) for optodes located on the toe and finger of the hand, respectively. Respective values in type 1 diabetes were higher: 3.00 ± 0.36 mm s(-1) and 3.10 ± 0.48 mm s(-1).