Hyperglycemia and vascular, glomerular dysfunction
abstract: Objectives: 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. Nitric oxide is a candidate for mediating hyperfiltration and the increased vascular permeability induced by diabetes.
Methods: Serum nitric oxide concentrations were assessed in 30 children and young adolescent with type 1 diabetes, 15 with and 15 without microalbuminuria compared with a well-balanced group of healthy control subjects. In all subjects, glomerular filtration rate (GFR) was determined using Cockcroft formula.
Results: Our study showed that serum nitric oxide values were significantly higher in microalbuminuria diabetic patients than in the other 2 groups (group I versus group II; 46.7 ± 7.9 versus. 32.2 ± 6.1 µmol/l, P < 0.05; while group I versus group III; 46.7 ± 7.9 versus 25.4 ± 4.2 µmol/l, P < 0.02. GFR was significantly and positively related to albumin excretion rate (AER) levels (r2 = 0.75, P < 0.0001), whereas Serum nitric oxide was independently associated with both AER and GFR values (B = 2.086, P < 0.05, B = 1.273, P < 0.0085, respectively). This finding suggesting a strong link between circulating nitric oxide, glomerular hyperfiltration, and microalbuminuria in type 1 diabetic patients with early nephropathy. 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. HbA1c serum concentration was significantly and positively related to serum nitric oxide (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 nitric oxide generation and/or action.
In conclusion, we suggest that in type 1 diabetic patients with early nephropathy, chronic hyperglycemia is associated with an increased nitric oxide biosynthesis and action that contributes to generating glomerular hyperfiltration and persistent microalbuminuria.
author: Galal A. Khalaf*, Magdy MK Mahmoud**, Ashraf M. Osman***
address: Internal Medicine*, Pediatric** and Clinical Pathology*** departments, El-Minia University Hospital, El-Minia, Egypt.