Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0730345 (microalbuminuria)
 4,018 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hyperglycemia has been causally linked to vascular and glomerular dysfunction by a variety of biochemical mechanisms, including a glucose-dependent abnormality in nitric oxide (NO) production and action. NO is a candidate for mediating hyperfiltration and the increased vascular permeability induced by diabetes. Serum nitrite and nitrate (NO2-+ NO3-) concentrations were assessed as an index of NO production in 30 adolescents and young adults with type 1 diabetes, 15 with and 15 without microalbuminuria (albumin excretion rate [AER] between 20 and 200 microg/min), compared with a well-balanced group of healthy control subjects. In all subjects, glomerular filtration rate (GFR) was determined by radionuclide imaging. Our study showed that NO2- + NO3- serum content and GFR values were significantly higher in microalbuminuric diabetic patients than in the other 2 groups. GFR was significantly and positively related to AER levels (r2 = 0.75, P < 0.0001), whereas NO2- + NO3- serum content was independently associated with both AER and GFR values (beta = 2.086, P = 0.05, beta = 1.273, P = 0.0085, respectively), suggesting a strong link between circulating NO, glomerular hyperfiltration, and microalbuminuria in young type 1 diabetic patients with early nephropathy. Interestingly, mean HbA1c, serum concentration was significantly higher in microalbuminuric than in normoalbuminuric diabetic subjects (P < 0.05) and was independently associated with AER values, suggesting a role for chronic hyperglycemia in the genesis of diabetic nephropathy. Moreover, HbA1c serum concentration was significantly and positively related to NO2 + NO3 serum content (r2 = 0.45, P = 0.0063) and GFR values (r2 = 0.57, P = 0.0011), suggesting that chronic hyperglycemia may act through a mechanism that involves increased NO generation and/or action. In conclusion, we suggest that in young type 1 diabetic patients with early nephropathy, chronic hyperglycemia is associated with an increased NO biosynthesis and action that contributes to generating glomerular hyperfiltration and persistent microalbuminuria.
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PMID:Increased circulating nitric oxide in young patients with type 1 diabetes and persistent microalbuminuria: relation to glomerular hyperfiltration. 1090 86

Diabetic nephropathy is a leading cause of end-stage renal failure. Its incidence is higher and is increasing in persons of Indo-Asian and African-Caribbean (African-Asian) compared with those of white origin. Nitric oxide deficiency is associated with progressive renal disease. It was hypothesized that differences in the capacity to increase glomerular filtration (functional renal reserve) would exist between these racial groups in relation to nitric oxide availability. Patients with type 2 diabetes of African-Asian (n = 9) and white (n = 9) origin with microalbuminuria were studied under euglycemic conditions. Glomerular filtration, renal plasma flow, and clearance of the stable metabolites of nitric oxide, nitrite, and nitrate were measured before and after a renal vasodilatory stimulus of a mixed amino acid intravenous infusion. There were no significant differences in age, duration of diabetes, and baseline glomerular filtration (57.1 [14.1] versus 55.8 [10.1] yr; P = 0.82, 14.5 [10.2] versus 9.1 [7.0] yr; P = 0.19 and 125.9 [30.9] versus 127.2 [44.6] ml/min per 1.73 m(2); P = 0.94) between the African-Asian and white groups. Functional renal reserve, change in renal plasma flow, and percentage change in nitrate and nitrite clearance was significantly higher in the white compared with the African-Asian group (21.9 [45.7] versus -2.5 [28.2] ml/min per 1.73 m(2); P = 0.043, 155.8 [205.9] versus -90.1 [146.0]; P = 0.03 ml/min per 1.73 m(2) and 26.7 [85.1] versus -44.7 [16.9] %; P = 0.013, respectively). The differences in functional reserve were not confounded after adjustment for diabetes duration (P = 0.034). The data suggest that these patients with type 2 diabetes of African and Asian origin lose functional renal reserve earlier in the evolution of nephropathy than whites. The differences appear to be due to defective nitric oxide production or bioavailability and might explain some of the propensity to develop end-stage renal disease.
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PMID:Defective nitric oxide production and functional renal reserve in patients with type 2 diabetes who have microalbuminuria of African and Asian compared with white origin. 1156 11

The assessment of the postprandial state in diabetes mellitus has gained importance due to postprandial hyperglycemia being considered as an independent risk factor for cardiovascular disease. Hyperglycemia may contribute to vascular dysfunction through the alteration of the nitric oxide/cyclic guanosine monophosphate (NO/cGMP) pathway. The authors assessed the NO/cGMP pathway in the fasting and postprandial state in 20 type 1 diabetic patients (age: 34.1 +/- 2.6 years, body mass index (BMI): 24.1 +/- 1.3 kg/m (2), duration of diabetes: 16 +/- 2.2 years, HbA (1C): 8.3 +/- 0.4 %, [x +/- SEM], 10 without, 10 with late complications) and 20 matched control subjects (age: 39.7 +/- 1.9 years, BMI: 25.3 +/- 1.1 kg/m (2)). In the fasting state NO end product (nitrite/nitrate) levels did not differ between the diabetic and control group, cGMP levels were found to be significantly lower in the diabetic group (2.5 +/- 0.2 vs. 4.6 +/- 0.6 nmol/l, p = 0.01). A higher level of lipid peroxidation end products (TBARS) was found in diabetic subjects (6.7 +/- 0.4 vs. 5.0 +/- 0.3 micro mol/l, p = 0.004). The diabetic subgroup without late complications had significantly higher nitrite/nitrate levels compared to the patients with complications (57.8 +/- 6.6 vs. 30.4 +/- 4.3 micro mol/l, p = 0.006), their TBARS and cGMP levels were similar. The control subjects responded to the test meal with an increase in the cGMP levels (4.6 +/- 0.6 to 5.5 +/- 0.6 nmol/l, p = 0.02), while in the diabetic group no change was detected. Postprandial nitrite/nitrate levels decreased in both groups, they were significantly lower in the diabetic group. There was no difference between postprandial nitrite/nitrate, cGMP, or glucose levels in the diabetic subgroups. Postprandial glucose levels showed a significant negative correlation with cGMP levels in the diabetic group (r = - 0.50, p = 0.02). The results suggest that in subjects with type 1 diabetes mellitus NO might have an impaired ability to induce cGMP production in the fasting state prior to the development of late specific complications or microalbuminuria under hyperglycemic conditions. Postprandial hyperglycemia is suggested to interfere with endothelial NO action, as shown by the decreased nitrite/nitrate and unchanged cGMP plasma levels in the diabetic group. The impairment of the NO/cGMP pathway both in the fasting and postprandial state that was shown in patients without diabetic complications may be an early sign of hyperglycemia induced vascular damage in type 1 diabetes mellitus.
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PMID:Impairment of the NO/cGMP pathway in the fasting and postprandial state in type 1 diabetes mellitus. 1514 72