A noninvasive single injection technique for the measurement of glomerular filtration rate (GFR) using technetium99m diethylene triamine pentaacetic acid (DTPA) was developed for use in the rat. GFR measurements obtained by the technique correlated well with those obtained by Cr51 EDTA infusion (R = 0.95, n = 7). The coefficient of variation was 8.4%. GFR was measured over 4 weeks in diabetic and control rats. GFR increased with time in both groups, with no difference between the groups; however, when corrected for body weight, diabetes was associated with an increased GFR (diabetic 13.6 +/- 1.7 vs. control 10.4 +/- 0.1 ml/min/kg p less than 0.001). Insulin treated rats had higher GFRs than untreated diabetics (p less than 0.05), but GFR/kg was reduced to that of nondiabetic controls. High protein intake in diabetic rats caused an increase in GFR after 1 week of diabetes, but this was not sustained by the fourth week. Genetic hypertension and angiotensin converting enzyme (ACE) inhibition with ramipril had no effect on GFR in diabetic rats. We conclude that serial measurement of GFR in the diabetic rat is accurate and reproducible. Genetic hypertension, high protein intake, and ACE inhibition have little effect on GFR in experimental diabetes.

Angiotensin-Converting Enzyme Inhibitors↗

PubMedDate not supplied

Intermittent diabetic microalbuminuria: association with blood pressure, glycemic control, and protein intake.

The factors associated with intermittent microalbuminuria were studied over 7 years in 49 Type I and 53 Type II diabetics who had normal initial albumin clearance. Fasting plasma glucose, HbA1, 24 hour urinary glucose, blood pressure, protein intake (24 hour urinary urea), and the renal clearance of albumin, transferrin, and IgG, as well as total proteinuria, were assessed every 3-6 months. Fifteen Type I and 11 Type II diabetics had 40 and 31 episodes, respectively, of intermittent microalbuminuria, defined as an albumin clearance greater than 11 nl/sec, without progressing to persistent microalbuminuria. Rises in transferrin and IgG clearance paralleled albumin clearance in both Type I and Type II diabetics. There were no significant changes in blood pressure or glycemic control during episodes of intermittent microalbuminuria. However, in Type I diabetics, intermittent microalbuminuria was associated with higher levels of urinary urea excretion. This study raises the possibility that increased protein intake may participate in the development of nephropathy in Type I diabetes.

Adult↗

PubMedDate not supplied

In vitro and in vivo antioxidant properties of gliclazide.

Diabetes is a state of increased oxidant stress and there is evidence that oxidation may play a role in the genesis of complications. Gliclazide, a sulfonylurea hypoglycemic drug, has been shown to possess free radical scavenging properties. This study examined the effects of in vitro supplementation with gliclazide and other sulfonylureas as on low-density lipoprotein (LDL) oxidation and the total plasma antioxidant capacity (TPAC). In a separate study, the effects of 10 months of oral gliclazide therapy on oxidative parameters were assessed in 44 type 2 diabetic patients. Gliclazide, but not glibenclamide, glimepiride, glipizide or tolbutamide, inhibited LDL oxidation and enhanced TPAC. With the addition of 1 microM gliclazide, oxidation lag time increased from 53.6+/-2.6 to 113.6+/-5.1 min (p<0.001), and TPAC increased from 1. 09+/-0.11 to 1.23+/-0.11 mM (p<0.01). Administration of either modified release or standard gliclazide to type 2 diabetic patients resulted in a fall in 8-isoprostanes, a marker of lipid oxidation, and an increase in the antioxidant parameters TPAC, SOD and thiols. These studies show that gliclazide possesses antioxidant properties that produce measurable clinical effects at therapeutic doses.

Antioxidants↗

PubMedDate not supplied

Effect of anti-oxidant treatment and cholesterol lowering on resting arterial tone, metabolic vasodilation and endothelial function in the human forearm: a randomized, placebo-controlled study.

1. The aim of the present study was to determine whether anti-oxidant therapy with vitamin E and/or cholesterol-lowering therapy with simvastatin would augment resting forearm blood flow (FBF) and metabolic vasodilation in response to exercise and improve endothelial function in young patients with hypercholesterolaemia. 2. Endothelium-dependent and -independent, nitric oxide (NO)-mediated vasodilation have been shown to be impaired in young, otherwise healthy subjects with hypercholesterolaemia. Recent experimental and clinical studies suggest that vascular function may be improved with anti-oxidant or cholesterol- lowering therapy, although these treatments may be synergistic. 3. We compared FBF at rest, in response to isotonic exercise, the endothelium-dependent vasodilator acetylcholine (ACh), the endothelium-independent vasodilator sodium nitroprusside (SNP) and the NO synthase inhibitor NG-monomethyl-L-arginine (L-NMMA) in 26 young, otherwise healthy volunteers (mean (+/-SD) age 29+/-7 years; 14 female, 12 male) with hypercholesterolaemia, before and after 6 months treatment with vitamin E, simvastatin and/or placebo. Treatment was randomized, double-blinded in a 2 x 2 factorial design. Forearm blood flow was measured using venous occlusion plethysmography. 4. Vitamin E therapy increased plasma alpha-tocopherol from 39.5+/-9.6 to 75.7+/-33.8 micromol/L (P < 0.001). Simvastatin reduced total cholesterol from 6.9+/-1.7 to 4.9+/-0.8 mmol/L and low- density lipoprotein (LDL) from 4.8+/-1.7 to 3.0+/-0.7 mmol/L (both P < 0.001), although total and LDL-cholesterol also decreased slightly in the placebo group. Vitamin E increased resting FBF from 2.1+/-0.3 to 2.4+/-0.3 mL/100 mL per min (P = 0.04) and decreased resting forearm vascular resistance from 42.1+/-4.2 to 36.1+/-3.4 units (P = 0.01), but the reduction in resting FBF with L-NMMA was not affected. Vasodilation in response to isotonic exercise, ACh and SNP was similar before and after treatment in the placebo, vitamin E, simvastatin and in the combined vitamin E-simvastatin groups. NG-Monomethyl-L-arginine infusion reduced resting FBF and functional hyperaemia in response to exercise and these responses were not altered by treatment. 5. These data suggest that while vitamin E therapy augments resting FBF and reduces forearm vascular resistance in young hypercholesterolaemic subjects, these effects may not be via NO-dependent pathways. Metabolic vasodilation and responses to the NO-mediated vasodilators ACh and SNP were not favourably affected by anti-oxidant or cholesterol-lowering therapy, either alone or in combination.

Adult↗

PubMedDate not supplied

Progression of proteinuria in type 1 and type 2 diabetes.

A longitudinal study evaluating the time course of the transition from normal to microalbuminuria, and then on to macroalbuminuria, was made over a mean period of 7 years in a cohort of 52 patients with Type 1 diabetes and 61 patients with Type 2 diabetes. Transient episodes of micro- and macroalbuminuria were often observed before the ultimate development of persistent Albustix-positive proteinuria. The transition from normal to microalbuminuria and from micro- to macroalbuminuria was characterized by rises in renal albumin clearance accompanied by lesser rises in total proteinuria. Seven patients with Type 1 and 12 with Type 2 diabetes showed evidence of progression, the interval for the transition from normal to macroalbuminuria varying from 3 to 5 years. In Type 1 diabetic patients, the development of micro- and macroalbuminuria was associated with a decline in renal function and a rise in systolic blood pressure without a significant change in blood glucose control. In Type 2 diabetic patients, the development of microalbuminuria was associated with a small decline in renal function but no change in blood pressure or blood glucose control. It is concluded that the transition from normal to micro- and on to macroalbuminuria may be more rapid then previously reported and varies considerably among individuals.

Adult↗

PubMedDate not supplied

Microalbuminuria: prognostic and therapeutic implications in diabetes mellitus.

Thirty years following the development of the first radioimmunoassay for albumin, microalbuminuria is widely acknowledged as an important predictor of overt nephropathy in patients with Type 1 diabetes and of cardiovascular mortality in Type 2 diabetes. In addition, there is accumulating evidence to suggest that diabetic patients with microalbuminuria may have more advanced retinopathy, higher blood pressure, and worse dyslipidaemia than patients with normal albumin excretion rates. Recent studies have focused on the role of intervention, principally with antihypertensive therapy and intensive glycaemic control, in reducing microalbuminuria. While successful in reducing urinary albumin excretion it remains to be established whether such therapies will be translated into a reduction in renal failure and decreased cardiovascular morbidity and mortality.

Albuminuria↗