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Biomedical subjects

M J Wiseman

Publications and source records attributed to M J Wiseman.

At least 19 recordsLinked to original sources
PubMed1996

Glomerular hyperfiltration in the prediction of nephropathy in IDDM: a 10-year follow-up study.

Glomerular hyperfiltration has been proposed as an independent risk factor for the development of diabetic nephropathy in patients with IDDM. In a case-controlled prospective study of IDDM patients without albuminuria, serial glomerular filtration rate (GFR) measurements were performed over an observation period of 10 years. A group of 25 IDDM patients (20 men, 5 women; initial age, 29 [17-49] years) with glomerular hyperfiltration (GFR >135 ml x min(-1) x 1.73 m(-2)) were matched for age, sex, and duration of diabetes with 25 IDDM patients (20 men, 5 women; initial age, 30 [17-48] years) with glomerular normofiltration (GFR 83-135 ml x min(-1) x 1.73 m(-2)). GFR, urinary albumin excretion rate (AER), blood pressure, and glycated hemoglobin were measured at baseline and at 5, 8, and 10 years. The two groups had similar entry levels of blood pressure, AER, and glycated hemoglobin. Metabolic control was similar in the two groups during follow-up. The final GFR remained higher in the group with hyperfiltration (122 [109-135] vs. 103 [95-111] ml x min(-1) x 1.73 m(-2); P = 0.02) despite a nonsignificantly faster rate of fall of GFR compared with that of the control group (2.54 [1.20-3.88] vs. 1.50 [1.01-1.99] ml x min(-1) x year(-1); P = 0.14). A similar number of patients in each group progressed to either microalbuminuria or macroalbuminuria (n = 4 vs. n = 3) or developed hypertension (blood pressure, >160/95 mmHg; n = 3 vs. n = 4). End-of-study AER was, however, higher in the group with hyperfiltration (geometric mean [95% CI]: 18.9 [11.3-31.6] vs. 11.0 [8.1-15.0]; P = 0.05), and baseline glomerular hyperfiltration was an independent determinant of end-of-study blood pressure (P = 0.04). The strongest predictors of end-of-study AER and blood pressure were their baseline values (P < 0.04 and P < 0.01, respectively). In conclusion, levels of AER and blood pressure are the main risk factors for renal outcome, while glomerular hyperfiltration appears to play a lesser role.

Adolescent↗
PubMed1989

Glomerular hyperfiltration and urinary prostaglandins in type 1 diabetes mellitus.

In order to determine whether glomerular hyperfiltration in diabetes is related to renal prostaglandin production we have studied the urinary excretion of PGE2, 6-keto-PGF1 alpha, and TXB2 in two sex, age and duration of diabetes matched groups of 9 and 10 Type 1 diabetic patients with either normal (mean 121, range 105-129 ml min-1 1.73 m-2) or supranormal glomerular filtration rate (154, 135-206 ml min-1 1.73 m-2). A group of 15 matched healthy volunteers served as control subjects. Urine was collected overnight for an uninterrupted period of at least 6 h. All studies in the patients were performed during insulin-induced sustained euglycaemia to prevent the confounding effect of variable degrees of blood glucose control on urinary prostaglandin excretion. Blood pressure was normal in all subjects. Urinary excretion of 6-keto-PGF1 alpha was significantly higher in the patients with glomerular hyperfiltration (median 17.1, range 4.5-33.6 ng h-1) than in those without (8.8, 1.5-13.8 ng h-1; p less than 0.05) or in normal control subjects (9.6, 5.2-15.5 ng h-1; p less than 0.05). No significant differences were found in the excretion rates of PGE2 and TXB2 between the three groups. Under conditions of controlled plasma glucose and insulin concentrations the urinary excretion of 6-keto-PGF1 alpha, the stable breakdown product of PGI2, a compound of endothelial, possibly glomerular, origin was elevated only in the diabetic patients with glomerular hyperfiltration.

6-Ketoprostaglandin F1 alpha↗
PubMed1987

Raised arterial pressure in parents of proteinuric insulin dependent diabetics.

Arterial pressure is raised early in the subset of insulin dependent diabetics at risk of later development of progressive renal failure, suggesting that liability to arterial hypertension may play a part in the aetiology of diabetic kidney disease. Evidence for a genetic basis was therefore sought by measuring the blood pressures of the 26 surviving parents of 17 insulin dependent diabetic patients with proteinuria and comparing them with those of the parents of 17 matched insulin dependent diabetic patients without proteinuria selected from the same cohort. Systolic and diastolic pressures were significantly higher in parents of the proteinuric (mean (SD) 161 (27)/94 (14) mm Hg) than in parents of the non-proteinuric patients (146 (21)/86 (11) mm Hg). The difference between the sample mean blood pressures was 15 mm Hg (95% confidence interval 3.3 to 26.7 mm Hg) for systolic pressure and 8 mm Hg (95% confidence interval 0.8 to 15.2 mm Hg) for diastolic pressure. These differences were independent of age, sex, and adiposity. There was a significant correlation between the mean arterial pressures in the proteinuric patients and the higher mean blood pressure in their parents. High blood pressure in non-diabetic parents may be a marker of susceptibility to clinical nephropathy in their insulin dependent diabetic offspring.

Adolescent↗
PubMed1987

Changes in renal function in response to protein restricted diet in type 1 (insulin-dependent) diabetic patients.

Glomerular filtration rate, renal plasma flow and urinary albumin excretion rate were measured during insulin-induced euglycaemia in 12 male Type 1 (insulin-dependent) diabetic patients after a 3-week period of low protein diet (45 g/day) or a similar period on unchanged conventional diet (103 g/day). No changes in glycaemic control, indicated by home blood glucose profiles and serum fructosamine concentration, or in arterial pressure, were noted on either diet. On low protein diet, glomerular filtration rate was lower (p less than 0.001) in all patients, but there was no difference in renal plasma flow between low protein diet and normal protein diet; filtration fraction fell significantly on low protein diet (p less than 0.001). Fractional clearance of albumin was also lower (p less than 0.05) on low protein diet. This study suggests that reduction of dietary protein induces, independently of changes in plasma glucose and arterial pressure, modifications in glomerular filtration rate, filtration fraction and fractional clearance of albumin, which may be associated with a beneficial effect on the evolution of diabetic renal disease.

Adult↗
PubMed1987

Glomerular response mechanisms to glycemic changes in insulin-dependent diabetics.

Glomerular filtration rate (GFR) and renal plasma flow (RPF) were measured by constant inulin and PAH infusion during euglycemia and intravenous dextrose-induced moderate hyperglycemia in seven insulin-dependent diabetics with persistently elevated GFR, seven diabetics with normal GFR, and in six normal control subjects. In euglycemia, RPF was higher and calculated renal vascular resistance (RVR) lower in the hyperfiltering than the normofiltering group (P less than 0.05 for both variables), but filtration fraction (FF) was similar in all groups. During hyperglycemia, mean GFR rose significantly from 157 +/- 20 to 174 +/- 30 ml/min/1.73 m2 (11.9%; P less than 0.05) in the hyperfiltering group only. There was no statistically significant change in mean GFR in the normofiltering diabetic (116 +/- 6 vs. 114 +/- 13 ml/min/1.73 m2) and the normal control groups (117 +/- 15 vs. 113 +/- 14 ml/min/1.73 m2). RPF and FF rose by 5.8% and 9.2%, respectively, in the hyperfiltering group only, with no change in the normofiltering or normal control groups. No change in RVR was found in any group. Total tubular sodium reabsorption was higher during euglycemia in the hyperfiltering diabetics (P less than 0.01), and rose significantly during hyperglycemia (P less than 0.05) in this group only. Overnight euglycemia did not remove the increased glomerular filtration and flow of hyperfiltering diabetics. Hyperglycemia further accentuated hyperfiltration by elevating renal plasma flow and filtration fraction.

Adult↗
PubMed1987

Effect of protein-restricted diet on renal response to a meat meal in humans.

To study the influence of preceding dietary protein intake on the renal response to a protein meal we examined renal hemodynamic and excretory responses to a meat meal in six normal human subjects either taking their normal-protein diet (NPD, 75 +/- 5 g/day) or after 3 wk of a low-protein diet (LPD, 43 +/- 3 g/day; P less than 0.005). Glomerular filtration rate (GFR) was lower on LPD than on NPD (107 +/- 7 vs. 124 +/- 5 ml X min-1 X 1.73 M-2, respectively; P less than 0.01), as was renal plasma flow (RPF) (NPD, 666 +/- 44; LPD, 605 +/- 43 ml X min-1 X 1.73 M-2; P less than 0.05). Filtration fraction (FF) was not different (NPD, 0.19 +/- 0.01; LPD, 0.18 +/- 0.01). Urinary excretion of albumin was also lower after LPD than NPD (2.1 +/- 0.5 vs. 4.2 +/- 0.8 micrograms/min; P less than 0.05). After an 80-g protein meat meal, GFR rose to a ceiling significantly higher on NPD than on LPD (132 +/- 4.8 vs. 120 +/- 5.2 ml X min-1 X 1.73 M-2; P less than 0.02), even though the percent changes were greater on LPD than on NPD (12.7 +/- 3.3 vs. 6.6 +/- 1.5%, respectively; P less than 0.05). There was a rise in RPF that was entirely attributable to a fall in renal vascular resistance, and FF did not change. On both diets, oral protein loading produced a 200-300% increase in the urinary excretion and fractional clearance of albumin and IgG, but failed to alter that of beta 2-microglobulin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Dietary composition and renal function in healthy subjects.

Increments in dietary protein intake can increase glomerular filtration rate (GFR) in humans, and the glomerular hyperfiltration induced by high protein intake has been incriminated in the progression of glomerulosclerosis related to age and a number of renal diseases. GFR (as 51Cr-EDTA clearance) was measured in 18 vegans, 16 lactovegetarians and 18 omnivorous control subjects, matched for age. Omnivores ate significantly more total protein and protein of animal origin than the other two groups. Vegetable protein comprised 100% of the vegans' daily protein intake and 64% of the lactovegetarians', both significantly higher than the omnivores' (32%). Vegans and lactovegetarians also ate more carbohydrate and fibre than omnivores, although fat intake was similar. Mean GFR was significantly lower in the vegans than in the omnivores (100 +/- 13 vs. 113 +/- 16 ml/min/1.73 m2; p less than 0.04) and was intermediate in the lactovegetarians (105 +/- 16 ml/min/1.73 m2). Omnivores had significantly higher mean urinary albumin excretion rate (p less than 0.05) than vegans, and higher mean diastolic blood pressure than both vegans and lactovegetarians (p less than 0.01). The vegan diet is associated with glomerular and systemic haemodynamic changes which may be beneficial in the prevention of glomerular sclerotic changes in health and disease.

Albuminuria↗
PubMed1985

Effect of blood glucose control on increased glomerular filtration rate and kidney size in insulin-dependent diabetes.

To investigate the relation between blood glucose control on the one hand and an increased glomerular filtration rate and enlarged kidneys on the other, we studied 12 patients with insulin-dependent diabetes and an increased glomerular filtration rate for a year after they were randomly assigned either to continuous subcutaneous insulin infusion or to unchanged conventional therapy. Glycemic control, measured by mean plasma concentrations of glucose and glycosylated hemoglobin, was rapidly and significantly improved (P less than 0.001) in the pump group but did not change in the conventional-treatment group. In the pump group, the glomerular filtration rate fell significantly in the study period (P less than 0.001) and became normal in four of the six patients. It did not change in the conventional-treatment group. There was no change in kidney volume in either group. At the end of a year, a return to conventional insulin treatment in the pump group resulted in both metabolic deterioration and a significant rise in the mean glomerular filtration rate toward base-line values. We conclude that in patients with established insulin-dependent diabetes, strict glycemic control normalizes the glomerular filtration rate, although the kidneys may remain enlarged.

Adult↗
PubMed1985

The glomerular hyperfiltration of diabetes is not associated with elevated plasma levels of glucagon and growth hormone.

Plasma concentrations of glucagon, growth hormone and glucose were measured hourly during an ordinary treatment day in 11 Type 1 (insulin-dependent) diabetic patients with high glomerular filtration rate, 11 Type 1 diabetic patients with normal glomerular filtration rate matched for age, diabetes duration and sex, and five healthy control subjects, simultaneously with the measurement of the glomerular filtration rate using 51Cr EDTA clearance. Plasma glucagon profiles were not statistically distinguishable (p = 0.49) from control values in either group, although they were somewhat lower in the hyperfiltering group. Plasma growth hormone values were higher than control (p = 0.07) in both diabetic groups, but were not different between these two groups (p = 0.94). All indices of glycaemic control (glycosylated haemoglobin, urinary glucose excretion, and plasma glucose concentration) were higher in the hyperfiltering group, although no single index reached statistical significance. No correlations between concentrations of these substances and glomerular filtration rate were found. Elevated plasma concentrations of glucagon and growth hormone do not characterise those diabetic patients with high glomerular filtration rate.

Adolescent↗