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Biomedical subjects

H Keen

Publications and source records attributed to H Keen.

At least 91 records · Page 5Linked to original sources
PubMed1988

Renal response to restricted protein intake in diabetic nephropathy.

Proteinuria in diabetes is associated with progressive glomerular damage. We studied the effects of 3-wk dietary protein restriction on proteinuria and renal function in 10 insulin-dependent diabetic men with diabetic nephropathy. Patients were randomly assigned by a crossover design to 40-g low-protein diet (LPD) or usual-protein diet (UPD). Glomerular filtration rate and renal plasma flow were measured by inulin and p-aminohippurate clearance at the end of each period under conditions of sustained euglycemia. Total calorie intake, body weight, serum albumin and total protein concentrations, hematocrit, blood pressure, and glucose control were similar during the two diets. Achieved protein intake was 46 +/- 3 g/day during LPD and 81 +/- 4 g/day during UPD (P less than .001). Urinary urea appearance and plasma urea were significantly lower on LPD. Median total urinary protein was reduced from 3.9 g/day (range 0.5-12.3) on UPD to 2.4 (range 0.2-9.0) on LPD (P less than .006), and there was a significant fall in the median fractional clearance of albumin from 2.0 x 10(-4) (range 0.1-90.9) on UPD to 1.0 x 10(-4) (range 0.1-51.4) on LPD and IgG from 2.1 x 10(-5) (range 0.2-238) to 1.5 x 10(-5) (range 0.1-77) (P less than .006 and P less than .02, respectively). The reabsorption rate of beta 2-microglobulin was similar on the two diets and glomerular filtration rate, renal plasma flow, and filtration fraction remained unchanged. Thus, short-term dietary protein restriction reduces diabetic proteinuria independently of blood glucose or systemic blood pressure changes by improving glomerular permselectivity.

Adult↗
PubMed1988

Effect of 6 months therapy with dexfenfluramine in obese patients: studies in the United Kingdom.

The efficacy of dexfenfluramine in inducing weight loss and its clinical acceptability were assessed in two studies carried out in a hospital obesity clinic and general practitioner's office. Seventeen patients who had gained an average of 0.7 +/- 1.9 kg during 12 weeks treatment with diet and placebo lost a mean of 2.9 +/- 0.5 kg after 12 weeks sequential treatment with dexfenfluramine 15 mg twice daily (p less than 0.001). In a second trial, 29 patients treated for 24 weeks with dexfenfluramine showed significantly increased, and continuing, weight loss after 24 weeks (7.0 +/- 0.8 kg) compared to that after 12 weeks of treatment (5.7 +/- 0.1 kg; p = 0.05). The incidence of side effects in both trials was lower than that reported in previous studies of racemic dl-fenfluramine. The clinically significant weight loss and low incidence of unwanted effects suggest that dexfenfluramine has a role in the treatment of refractory obesity.

Clinical Trials as Topic↗
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

Massive insulin resistance apparently due to rapid clearance of circulating insulin.

A 23-year-old insulin-dependent diabetic woman demonstrated increasing resistance to insulin administered by all routes, eventually requiring up to 20,000 units per day intravenously. Therapeutic trials of human and chemically modified insulin and of aprotinin were unsuccessful. Inappropriately low plasma free insulin levels (less than 60 mU/liter) during administration of extremely high insulin dosages (300 to 10,000 units per day) suggested that resistance was caused by rapid clearance of circulating insulin. There were several short periods of normal insulin sensitivity with hyperinsulinemia (more than 300 mU/liter) persisting long after intravenous insulin withdrawal, suggesting reentry to the circulation of intact, previously sequestered insulin. For four years, she has been treated with ambulatory continuous intravenous insulin infusion, which has been complicated by septicemia and central venous thrombosis. Her condition remains poorly controlled with documented intravenous insulin requirements of 2 to 20 units/hour.

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

Changes in blood pressure and body weight over ten years in men selected for glucose intolerance.

Relative changes in body weight and blood pressure over ten years of observation are reported in men recruited for a trial of therapy in relation to the natural history of glucose intolerance. Half were recommended a diet restricting carbohydrate to 120 g daily (diet group) and half were recommended to 'limit use of table sugar' (no diet). In both groups average weight and blood pressure fell over the 12 to 18 months after treatment allocation, the decline being proportionately greater for both variables in the diet group. Subsequently, average weight remained constant up to the end of the ten year study, but blood pressure levels rose, though remaining below baseline levels in the diet group. Statistical analysis of changes in blood pressure and weight between initial (pre-treatment) and third follow-up visit measurement indicated that the proportional change in blood pressure was related principally to change in weight, with little relation to initial level of blood pressure. Although a reduction in weight results in a fall in blood pressure, it does not necessarily prevent a subsequent age related increase in blood pressure.

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↗
PubMed1986

Intermittent clinical proteinuria and renal function in diabetes: evolution and the effect of glycaemic control.

The evolution of renal disease was studied in 12 insulin dependent diabetics selected for intermittent clinical proteinuria. After a run in period during which patients were studied three monthly for at least 12 months members of pairs of patients matched for age and duration of diabetes were allocated either to receive continuous subcutaneous insulin infusion or to continue with their usual conventional insulin injection therapy (controls) and studied three monthly for a further year. Mean (SEM) plasma glucose concentration and glycosylated haemoglobin (HbA1) value improved significantly in the insulin infusion group (glucose 10.1 (1.0) v 5.3 (0.3) mmol/l (182 (18) v 95 (5) mg/100 ml); HbA1 9.6 (0.8) v 7.6 (0.5)%; p less than 0.001 and p less than 0.005, run in v experimental periods) but not in the control group. Blood pressure was kept normal throughout. Glomerular filtration rate fell significantly in the insulin infusion and control groups throughout the study, from mean (SEM) baseline values of 114 (16) and 119 (15) ml/min/1.73 m2 to final values of 92 (15) and 95 (13) ml/min/1.73 m2 respectively (p less than 0.05 and p less than 0.01). The mean rate of decline in glomerular filtration rate did not change significantly in either group (run in v experimental periods: insulin infusion group 1.0 v 0.8 ml/min/month; controls 0.8 v 0.9 ml/min/month). Mean (SEM) plasma creatinine concentration rose slightly in the insulin infusion group only (93 (5) to 109 (11) mumol/l (1.1 (0.06) to 1.2 (0.1) mg/100 ml), 0.1 greater than p greater than 0.05; controls 94 (6) to 96 (6) mumol/l (1.1 (0.07) and 1.1 (0.07) mg/100 ml]. The urinary excretion rate of albumin varied widely and unpredictably throughout, while beta 2 microglobulin excretion remained normal and unchanged in both groups. Thus a at the stage of intermittent clinical proteinuria when albumin excretion rate is unpredictably variable (breaking through the "clinically positive" threshold only episodically) renal function, though still in the "normal" range, is already declining progressively; and the study failed to show that sustained improvement in mean glycaemia exerts a significant effect on this early deterioration of renal function.

Adult↗
PubMed1985

The Southall Diabetes Survey: prevalence of known diabetes in Asians and Europeans.

A house to house inquiry for patients with known diabetes was carried out in a defined area of Southall, west London, which contained over 34 000 Asians and 27 000 Europeans in the 1981 Census: 1143 diabetic patients were ascertained, of whom 761 were Asian and 324 European. The prevalence adjusted for age of known diabetes in Asians was at least 3.8 times higher than that in Europeans. For patients aged between 40 and 64 years it was at least five times higher, was over 12% in Asians aged 60-69, and over 8% in those aged 50-59. These data are important in planning for the care of diabetic patients in health districts with large Asian communities. The causes and later consequences of this exceptionally high prevalence require further study.

Adolescent↗