Microalbuminuria is associated with impaired arterial and venous endothelium-dependent vasodilation in patients with Type 2 diabetes.

BACKGROUND: Microalbuminuria in Type 2 diabetes is associated with arterial endothelial dysfunction, but the venous bed was never evaluated. AIM: To study the endothelial function in the venous and arterial bed in patients with Type 2 diabetes with normoalbuminuria or microalbuminuria. MATERIAL AND METHODS: We evaluated 28 patients with Type 2 diabetes, glycated hemoglobin (HbA(1c)) <7.5%, who were classified as normo- (albuminuria <30 mg/24 h; no.=16) or microalbuminuric (albuminuria 30-300 mg/24 h; no.=12). Venous and arterial endothelial function were assessed by the dorsal hand vein technique (venodilation by acetylcholine) and brachial artery flow-mediated vasodilation, respectively. RESULTS: Patients were normotensive (systolic arterial pressure: 131.1±10.6 mmHg) and on good metabolic control (HbA(1c): 6.6±0.6%). Microalbuminuric patients presented impaired venous (32.9±17.4 vs 59.3±26.5%; p=0.004) and arterial vasodilation (1.8±0.9 vs 5.1±2.4; p<0.001), as compared to normoalbuminuric patients. There was a negative correlation between acetylcholine-induced venodilation and albuminuria (r=-0.62; p<0.001) and HbA(1c) (r=-0.41; p=0.032). The same was observed between flow mediated arterial vasodilation and albuminuria (r=-0.49; p=0.007) and HbA(1c) (r=-0.44; p=0.019). Venous and arterial vasodilation was positively correlated (r=0.50; p=0.007). CONCLUSIONS: Both venous and arterial endothelial function are impaired in Type 2 microalbuminuric diabetics, in spite of good metabolic control, suggesting that other factors are involved in its pathogenesis.

Reduced cortical renal GLUT1 expression induced by angiotensin-converting enzyme inhibition in diabetic spontaneously hypertensive rats.

Diabetes in spontaneously hypertensive rats is associated with cortical renal GLUT1 and GLUT2 overexpression. Our objective was to evaluate the effect of the angiotensin-converting enzyme blockade on cortical renal GLUT1 and GLUT2 expression, urinary albumin and urinary TGF-beta1. Streptozotocin, 50 mg/kg, or citrate buffer (N = 16) was administered as a single injection into the tail vein in adult spontaneously hypertensive rats (approximately 260 g). Thirty days later, these diabetic spontaneously hypertensive rats received ramipril by gavage: 0.01 mg x kg(-1) x day(-1) (D0.01, N = 14), 1 mg x kg(-1) x day(-1) (D1, N = 9) or water (D, N = 11) for 15 days. Albumin and TGF-beta1 (24-h urine), direct arterial pressure, renal tissue angiotensin-converting enzyme activity (fluorometric assay), and GLUT1 and GLUT2 protein levels (Western blot, renal cortex) were determined. Glycemia and glycosuria were higher (P < 0.05) in the diabetic rats compared with controls, but similar between the diabetic groups. Diabetes in spontaneously hypertensive rats lowered renal tissue angiotensin-converting enzyme activity (40%), which was reduced further when higher ramipril doses were used. Diabetes associated with hypertension raised GLUT1 by 28% (P < 0.0001) and GLUT2 by 76% (P = 0.01), and both doses of ramipril equally reduced cortical GLUT1 (D vs D1 and vs D0.01, P < or = 0.001). GLUT2 levels were reduced in D0.01 (P < 0.05 vs D). Diabetes increased urinary albumin and TGF-beta1 urinary excretion, but the 15-day ramipril treatment (with either dose) did not reduce them. In conclusion, ramipril is effective in lowering renal tissue angiotensin-converting enzyme activity, as well as blocking cortical GLUT1 overexpression, which may be beneficial in arresting the development of diabetic nephropathy.

Reduced cortical renal GLUT1 expression induced by angiotensin-converting enzyme inhibition in diabetic spontaneously hypertensive rats

Diabetes in spontaneously hypertensive rats is associated with cortical renal GLUT1 and GLUT2 overexpression. Our objective was to evaluate the effect of the angiotensin-converting enzyme blockade on cortical renal GLUT1 and GLUT2 expression, urinary albumin and urinary TGF-¦Â1. Streptozotocin, 50 mg/kg, or citrate buffer (N = 16) was administered as a single injection into the tail vein in adult spontaneously hypertensive rats (~260 g). Thirty days later, these diabetic spontaneously hypertensive rats received ramipril by gavage: 0.01 mg¡¤kg-1¡¤day-1 (D0.01, N = 14), 1 mg¡¤kg-1¡¤day-1 (D1, N = 9) or water (D, N = 11) for 15 days. Albumin and TGF-¦Â1 (24-h urine), direct arterial pressure, renal tissue angiotensin-converting enzyme activity (fluorometric assay), and GLUT1 and GLUT2 protein levels (Western blot, renal cortex) were determined. Glycemia and glycosuria were higher (P < 0.05) in the diabetic rats compared with controls, but similar between the diabetic groups. Diabetes in spontaneously hypertensive rats lowered renal tissue angiotensin-converting enzyme activity (40 percent), which was reduced further when higher ramipril doses were used. Diabetes associated with hypertension raised GLUT1 by 28 percent (P < 0.0001) and GLUT2 by 76 percent (P = 0.01), and both doses of ramipril equally reduced cortical GLUT1 (D vs D1 and vs D0.01, P ¡Ü 0.001). GLUT2 levels were reduced in D0.01 (P < 0.05 vs D). Diabetes increased urinary albumin and TGF-¦Â1 urinary excretion, but the 15-day ramipril treatment (with either dose) did not reduce them. In conclusion, ramipril is effective in lowering renal tissue angiotensin-converting enzyme activity, as well as blocking cortical GLUT1 overexpression, which may be beneficial in arresting the development of diabetic nephropathy.

Thyroid volume is associated with family history of thyroid disease in pregnant women with adequate iodine intake: a cross-sectional study in southern Brazil.

UNLABELLED: Maternal euthyroidism is important for fetal neural development. For this reason, adequate iodine nutrition during pregnancy is an important public health objective and should be periodically revised. The objective of this study was to measure urinary iodine (UI) excretion and the factors associated with thyroid volume (TV), in a group of healthy pregnant women in southern Brazil, to evaluate iodine nutrition. The median UI of the 147 women was 224 microg/l (P25=164 microg/l and P75=286 microg/l). Serum levels of free T4 and thyroglobulin did not correlate with UI, but there was a weak inverse correlation between serum TSH levels and UI (r=-0.200; p=0.02). TV, calculated through ultrasound in 57 women, was significantly associated with family history of thyroid diseases (p=0.002) and BMI (p=0.03), but there was no association with UI, corrected or not for creatinine, serum free T4, TSH or thyroglobulin, current or past smoking, gestational age, parity or oral contraceptive. CONCLUSIONS: The healthy pregnant women studied had adequate iodine intake. In this situation, the main thyroid size determinants are probably genetic factors.

Increased renal GLUT1 abundance and urinary TGF-beta 1 in streptozotocin-induced diabetic rats: implications for the development of nephropathy complicating diabetes.

Increased expression of transforming growth factor beta-1 (TGF-beta 1) and glucose transporter (GLUT1) has been implicated in the genesis of diabetic nephropathy. The aim of this study was to evaluate GLUT1 protein levels in the renal cortex of a rat model of diabetes as well as its relationship to urinary albumin and TGF-beta1. Streptozotocin-injected rats (n = 13) and controls (n = 13) were compared for their urinary albumin, and TGF-beta 1 and for renal cortical and medullar GLUT1 protein abundance. GLUT1 protein content was determined by optical densitometry after Western blotting using an anti-GLUT1 antibody; urinary albumin was measured using electroimmunoassay, urinary TGF-beta 1 using ELISA. Forty-five days of diabetes resulted in increased albuminuria (p < 0.05), urinary TGF-beta 1 (p < 0.05) and GLUT1 protein abundance (p < 0.05). There was a positive correlation between urinary TGF-beta 1 and plasma glucose levels (r = 0.65, p < 0.05) and albuminuria (r = 0.72, p < 0.05). We concluded that 45 days of diabetes result in incipient diabetic nephropathy and increased cortical GLUT1 protein abundance. We speculate that the higher cortical GLUT1 protein levels in diabetes may amplify the effects of hyperglycemia in determining higher intracellular glucose in mesangial cells, thereby contributing to diabetes-related kidney damage.

Transforming growth factor-beta in the development of rat diabetic nephropathy. A 10-month study with insulin-treated rats.

We investigated the intrarenal distribution of transforming growth factor-beta 1 (TGF-beta 1) protein and the TGF-beta 1 mRNA levels in the glomeruli and renal cortex of Wistar rats with streptozotocin-induced diabetes before and after the onset of diabetic nephropathy. Monthly urinary albumin excretion, glomerular filtration rate, glomerular volume, renal histology and immunohistochemical reaction for type-I collagen were also studied. The results showed progressively higher glomerular immunohistochemical TGF-beta 1 staining in rats with a diabetes duration of 24 and 40 weeks which was correlated with albuminuria (r = 0.905, p < 0.01) and was temporally associated with the appearance of glomerular deposition of total and type-I collagen. The glomerular content of TGF-beta 1 mRNA was higher in rats diabetic for 20 weeks while lower cortical RNA-TGF-beta 1 levels were found in rats with a diabetes duration of 1-40 weeks. These data suggest that this polypeptide may be an important mediator of diabetic glomerulosclerosis.

Intensity-related exercise albuminuria in insulin dependent diabetic patients.

Normoalbuminuric insulin-dependent diabetic (IDDM) patients may present higher rates of urinary albumin excretion after submaximal exercise at a standard intensity. To evaluate whether the urinary albumin excretion of IDDM patients is increased after maximal and submaximal exercise when exercise intensities are adjusted according to individual lactate thresholds, 16 normoalbuminuric IDDM patients (mean time from diagnosis 8 years) and 13 normal controls exercised for 20 min at intensities corresponding to 90% of the first and second lactate thresholds and to maximal tolerance on different days. Urinary albumin excretion, blood lactate concentration, heart rate and blood pressure were measured. Metabolic and cardiovascular responses to submaximal and maximal exercise were similar for patients and controls. After exercise at 90% of the first lactate threshold neither patients or controls demonstrated significant changes in urinary albumin excretion. After exercise at 90% of the second lactate threshold both patients and controls demonstrated a similar increase in urinary albumin excretion. After maximal exercise both patients and controls demonstrated marked and similar elevation in the urinary albumin excretion. There was a significant correlation (r = 0.74, P < 0.001) between blood lactate levels at the end of exercise and the decimal logarithm of post-exercise urinary albumin excretion of the diabetic patients. Thus, when exercise intensities are adjusted for lactate thresholds, normoalbuminuric IDDM patients present normal intensity-related urinary albumin excretion during exercise. These data suggest that previously observed differences in exercise induced albuminuria in IDDM patients might be related to inappropriate standardization of submaximal exercise intensities.