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Biomedical subjects

H Keen

Publications and source records attributed to H Keen.

At least 145 records · Page 8Linked to original sources
PubMed1983

Determinants of the penetration of proteins through the glomerular barrier in insulin-dependent diabetes mellitus.

To investigate the determinants of the glomerular filtration of proteins in insulin-dependent diabetic patients we studied the fractional clearance of albumin (theta Alb) and IgG (theta IgG) and the selectivity index (SI = IgG clearance/Alb clearance) in 32 subjects with macroproteinuria (albustix positive), in 29 subjects with microproteinuria (albustix negative), and in 24 healthy control subjects. Fractional clearances of both albumin and IgG were higher in macroproteinuric than in microproteinuric patients, with both groups having higher values than controls (all P less than 0.001). In microproteinuric patients with albumin excretion rate (AER) not exceeding 60 micrograms/min, there was a highly significant correlation between the clearance of albumin and that of IgG. The SI was normal for AERs up to 30 micrograms/min, but above that albumin filtration increased disproportionately and SI progressively fell. In insulin-dependent diabetics with macroproteinuria, there was a negative correlation between SI and glomerular filtration rate (GFR) (r = -0.68; P less than 0.001); the lower SI (0.133 +/- 0.06) at higher GFRs also was due to a preferential increase in albumin clearance. Selectivity was progressively lost as GFR declined, and the SI returned to normal values when GFR fell below 10 ml/min/1.73 m2; this was due to a progressively higher rise in the fractional clearance of IgG relative to albumin. We suggest that glomerular filtration of proteins is governed by different determinants at different stages of the disease. In microproteinurics with AER below 60 micrograms/min, increased intraglomerular pressure seems primarily responsible for the higher proportional filtration of both albumin and IgG.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1983

Changes in blood flow close to subcutaneous insulin injection sites in stable and brittle diabetics.

Photoelectric plethysmography (PPG) was used to investigate blood flow changes close to superficial subcutaneous injection sites. As a validation procedure, the PPG response to subcutaneous injection of a known hyperemic agent, prostaglandin E1 (10(-5) M), was shown to correlate strongly with subcutaneous blood flow changes estimated by the established technique of 133Xe washout. Changes in blood flow over the subcutaneous injection sites of insulin (Actrapid) and insulin diluent were measured by photoelectric plethysmography in six nondiabetics and in six stable and seven brittle insulin-dependent diabetics. In all subject groups, an acute increase in local blood flow was seen within 2 min of both insulin and diluent injections, probably caused by injection trauma. At diluent injection sites, this acute hyperemia faded rapidly, blood flow returning to preinjection levels within 15-20 min, and there was no further increase in blood flow in any of the subjects. Insulin injected into the nondiabetics and stable diabetics caused a pronounced increase in local blood flow, sustained for at least 60 min after injection. In the brittle diabetics, however, there was no prolonged local hyperemia, the response being significantly less than that seen in both the nondiabetics and the stable diabetics. Insulin-related hyperemia close to injection (or infusion) sites may be important in subcutaneous insulin absorption. Its near-absence in brittle diabetics may contribute to the impaired response to subcutaneous insulin characteristic of these patients.

Adult↗
PubMed1983

The Bedford Survey: observations on retina and lens of subjects with impaired glucose tolerance and in controls with normal glucose tolerance.

After the Bedford Survey observations were made upon retina and lens in borderline diabetics (persons with impaired glucose tolerance) and in age and sex matched controls with normal glucose tolerance. Seven years after the Survey, the prevalence of retinal abnormalities ("microaneurysms" and "exudates") was similar in each group. Of 145 initially borderline diabetics examined 10 years after the Survey, 25 had worsened to diabetes. Only two of the total group had "micro-aneurysms" present and the maximum recorded in any eye was three. Lens opacities were of similar frequency in both groups shortly after the Survey and at the seven year follow-up examination. By contrast, 24% of 79 diabetics newly diagnosed during the Survey had "microaneurysms" recorded five years later. These results further justify the diagnostic category of impaired glucose tolerance, which, at least when discovered by population screening, carries no risk of clinically apparent eye disease for at least ten years after ascertainment.

Aneurysm↗
PubMed1982

Biosynthetic human insulin in the treatment of diabetes. A double-blind crossover trial in established diabetic patients.

94 diabetic patients established on treatment with porcine (n = 47) or bovine (n = 47) insulin took part in a double-blind crossover trial, in which 6-week periods of treatment with the appropriate animal insulin were compared with periods of treatment with biosynthetic human insulin (BHI). 6 patients withdrew during the trial, in 3 cases because of hypoglycaemia while taking BHI. In bovine-insulin-treated patients, the mean glucose level (mean of seven capillary-blood samples over 1 day), the modified M index, and total daily insulin requirement were the same on BHI and bovine-insulin treatment. For porcine-insulin-treated patients, mean glucose level and the modified M index were slightly higher on BHI than on porcine-insulin treatment (9.7 vs 9.0 mmol/l and 79.6 vs 65.0, respectively), despite an average increase of 2.3 units/day of BHI after 6 weeks of such treatment. Hypoglycaemic episodes were not significantly more or less frequent on BHI in either group of patients. In both groups fasting blood glucose was higher during BHI treatment than during animal-insulin treatment (14.2 vs 12.8 mmol/l [bovine group]; 12.1 vs 9.6 mmol/l [porcine group]). In bovine-insulin-treated patients blood glucose before the evening insulin injection was higher on BHI than on bovine insulin (11.6 vs 10.0 mmol/l). BHI appears to be a safe alternative to porcine or bovine insulin. Differences in the pharmacokinetics of BHI may account for the observed differences in blood-glucose responses.

Adult↗
PubMed1982

Microalbuminuria as a predictor of clinical nephropathy in insulin-dependent diabetes mellitus.

The overnight urinary albumin excretion rate (AER) of 87 patients with insulin-dependent diabetes mellitus was measured in 1966-67, 14 years later information was obtained on 63 of the original cohort; those alive were restudied, and for those who had died relevant clinical information and case of death were recorded. The development of clinical diabetic nephropathy ('Albustix'positive proteinuria) was related to the 1966-67 AER values. Clinical proteinuria developed in only 2 of 55 patients with AER below 30 microgram/min but in 7 of 8 with AER between 30 and 140 microgram/min. The risk of clinical diabetic nephropathy in the latter group was twenty-four time higher than inthe former. 9.1% of patients with AER below 30 microgram/min had died, compared with 37.5% with higher AER. The two groups did not differ significantly in age, sex composition, and initial blood pressure. Mean duration of diabetes was longer, but not significantly so, in those with AER above 30 microgram/min. Thus, elevated levels of microalbuminuria strongly predict the development of clinical diabetic nephropathy. These levels of AER are potentially reversible, and their detection and treatment may prevent diabetic renal disease.

Adolescent↗
PubMed1982

The ten-year follow-up of the Bedford survey (1962-1972): glucose tolerance and diabetes.

In a 10-year prospective study of 241 people with 'borderline diabetes' (impaired glucose tolerance) identified by screening of the Bedford adult population, 36 (15%) worsened to diabetes and 128 (53%) substantially improved their glucose tolerance. The major predictor of worsening to diabetes was the level of blood glucose at baseline. This was statistically significant (p less than 0.05), independent of other factors, both for deterioration in the first and in the second five years of observation. Body mass index, a measure of adiposity, did not predict worsening to diabetes during the first five years, but was an independent and significant predictor of worsening during the second five years (p less than 0.05). The apparent effect of adiposity was complex, for it was also significantly related to improvement in glucose tolerance during the 10-year follow-up. Persons with impaired glucose tolerance are a heterogeneous group and with present knowledge the ability to predict metabolic deterioration is limited.

Age Factors↗
PubMed1982

The Bedford survey: ten year mortality rates in newly diagnosed diabetics, borderline diabetics and normoglycaemic controls and risk indices for coronary heart disease in borderline diabetics.

Mortality rates from coronary heart disease and from all causes have been ascertained over ten years in three groups of people participating in the Bedford Survey--newly-diagnosed diabetics, borderline diabetics and control subjects with normal glucose tolerance. Age corrected mortality rates, from all causes and coronary heart disease, were highest in the diabetics and intermediate in the borderline diabetics and in both groups were similar in men and women. When statistical allowance was made for baseline differences in age, blood pressure and obesity, female borderline diabetics still had a significantly increased risk over their controls of death from 'all causes'. Much of the difference appeared to be due to a relative excess of deaths due to coronary heart disease. It is concluded that borderline diabetes (or impaired glucose tolerance) is associated with a relatively greater increase in mortality risk in women than men. During the 10-year follow-up of the Bedford borderline diabetics, coronary heart disease morbidity and mortality rates were similar in men and women. Age at entry to the study was the major independent and significant predictor of mortality from all causes. The level of systolic blood pressure and current cigarette smoking at baseline were statistically significant predictors only of mortality due to coronary heart disease.

Adolescent↗
PubMed1982

Interrelationships of microangiopathy, plasma glucose and other risk factors in 3583 diabetic patients: a multinational study.

In a multinational study, fasting plasma glucose values in 3583 diabetic patients, aged 34-56 years, were related to the characteristics of these subjects and to the presence and severity of microangiopathy as ascertained by standardised methods. The patients were from nine different populations and ranged in number from 193 to 686 per population (London, Warsaw, Berlin (FRG), New Delhi, Tokyo, Havana, Oklahoma Indians, Arizona Pima Indians, and a national sample in Switzerland). In the total group, mean fasting plasma glucose was 8.1 mmol/l for those on diet alone, 9.7 mmol/l for those on oral agents, and 12.7 mmol/l for insulin-treated patients, of whom 25% had values exceeding 16.5 mmol/l. Since many variables were measured in each patient, it was possible to take into account many confounding factors in evaluating the relationship of plasma glucose levels to retinopathy and nephropathy.

Adult↗
PubMed1982

Safety of continuous subcutaneous insulin infusion: metabolic deterioration and glycaemic autoregulation after deliberate cessation of infusion.

To assess the rate of metabolic deterioration and potential risks of failure of continuous subcutaneous insulin infusion during basal insulin delivery, we deliberately stopped infusion in nine insulin dependent diabetics. Plasma glucose, blood 3-hydroxybutyrate and plasma free insulin were measured for 9 h whilst the patients remained supine and fasting. Mean plasma glucose remained unchanged at normal fasting levels for the first hour, then rose to plateau at about 10 mmol/l until the end of the experiment. The final plateau level of glucose varied from patient to patient; two C-peptide secreting diabetics plateaued at low glucose levels. In contrast, blood 3-hydroxybutyrate rose progressively, without plateauing. PLasma free insulin concentrations fell during the withdrawal period and there was a highly significant negative correlation between free insulin and 3-hydroxybutyrate. No patient was more than mildly unwell after 9 h of insulin deprivation. We conclude that under these experimental conditions there is glycaemic autoregulation and that ketones may sometimes be a more appropriate monitor of insulin deficiency or loss of diabetic control than is glucose. Accidental failure of continuous subcutaneous insulin infusion and interruption of basal delivery in resting and fasting diabetics will probably not cause dangerous metabolic or clinical deterioration.

3-Hydroxybutyric Acid↗
PubMed1982

High density lipoprotein subfractions in insulin-dependent diabetic and normal subjects.

Serum lipoproteins have been separated by preparative ultracentrifugation in randomly selected groups of insulin-dependent diabetics and in age- and sex-matched non-diabetic controls. The major high density lipoprotein (HDL) subclass; HDL2 (density (d) 1.063-1.125 kg X m-3) and HDL3 (d greater than 1.125) and the further fractions of HDL2:HDL2b (d 1.063-1.100) and HDL2a (d 1.100-1.125) were also separated and their cholesterol (C) concentrations determined. These diabetic men and women were relatively normolipaemic and the major difference from controls was a significantly raised total HDL-C in men which was confirmed by a separate chemical precipitation method. This increase was associated with a significant rise in HDL2a-C and in total HDL2-C concentration. The non-significant increase in diabetic women compared to men was associated with poorer metabolic control. Among factors influencing serum HDL2-C concentration, the most important was the negative association with the level of very low density lipoprotein-triglycerides. Although insulin-dependent diabetics have an increased risk of atherosclerotic coronary heart disease (CHD), this is not reflected in their HDL subfraction-C distribution which, if present in non-diabetics, would be expected to confer protection from CHD.

Adult↗
PubMed1982

Proteinuria in diabetes mellitus: role of spontaneous and experimental variation of glycemia.

The excretion rates of albumin, IgG and beta 2-microglobulin were studied in insulin-dependent diabetic patients with (Albustix positive) and without (Albustix negative) clinical proteinuria and in a group of nondiabetic controls. In patients negative for clinical proteinuria, the mean excretion rate of albumin and IgG was increased but that of beta 2-microglobulin was normal. HbA1, a measure of excess glycemia, was positively correlated with both albumin and IgG urinary excretion rates. Vigorous correction of glycemic control significantly reduced IgG excretion in nine patients. In patients positive for clinical proteinuria, albumin and IgG clearances were inversely correlated with GFR, the filtration of IgG increasing relatively more than that of albumin as GFR declined. A negative hyperbolic correlation was found between GFR and beta 2-micro-globulin excretion. In this group HbA1 was unrelated to excretion rates or clearances of albumin and IgG. In clinically proteinuric patients, long-term correction of hyperglycemia by continuous subcutaneous insulin infusion failed to check the increasing albumin and IgG filtration. The microproteinuria of diabetes is glomerular in origin, is influenced by prevailing glycemia, and is reversible by vigorous glycemic control. In the clinically proteinuric phase, by contrast, selectivity is progressively lost and, as GFR falls, proteinuria becomes of a mixed glomerular and tubular origin. There is no evident association with prevailing glycemia, and metabolic near-normalization dose not appear to affect progression over the period of observation considered. This study suggests that clinical proteinuria denotes the installation of a self-maintaining process, largely independent of the diabetic metabolic disturbance which gave rise to it. Prevention of clinical diabetic nephropathy by metabolic correction may be achievable only in the phase of early microproteinuria.

Adult↗