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Biomedical subjects

H Keen

Publications and source records attributed to H Keen.

At least 127 records · Page 7Linked to original sources
PubMed1984

Threshold effect of plasma glucose in the glomerular hyperfiltration of diabetes.

Glomerular filtration rate (GFR) is abnormally high in some, but not all, insulin-dependent diabetic patients. The potential importance of this hyperfiltration lies in its possible link with later severe diabetic kidney disease. Inadequate glycaemic control is closely related to hyperfiltration but the mechanisms of the association are obscure. GFR and prevailing plasma glucose concentration were examined in a group of insulin-dependent diabetics without clinical proteinuria and in a group of non-diabetics, and their relationships observed using linear and multiple regression analysis. A positive correlation (r = 0.30, p less than 0.05) is found between mean plasma glucose concentration and GFR up to a mean plasma glucose level of approximately 13.5 mmol/l. Glycaemia in excess of this degree tends to be associated with a lower GFR. Multiple regression analysis confirmed the independence of plasma glucose as a determinant of GFR (p less than 0.05) at concentrations below 13.5 mmol/l. GFR declined significantly with age, but independently of diabetes duration, in the diabetic group (r = -0.48, p less than 0.001). GFR in the control group showed a statistically non-significant decline with age.

Adolescent↗
PubMed1984

Metabolic effects of physical exercise in insulin-dependent diabetics controlled by continuous subcutaneous insulin infusion or conventional injection therapy.

The metabolic and hormonal response to moderately severe exercise 2 h after breakfast was assessed in 8 insulin-dependent diabetics during conventional insulin injection therapy and after 3 weeks of continuous sc insulin infusion. Blood glucose fell from 12.1 to 4.4 mmol/l on injection therapy; this was accompanied by a significant rise (P less than 0.05) in free insulin to 57 mU/l. On infusion therapy plasma glucose fell and stabilised at 3.6 mmol/l from pre-exercise levels of 7.1 mmol/l, while free insulin level was unchanged at the end of the exercise period (31 mU/l). The fall in blood glucose on injection therapy was accompanied by an exaggerated growth hormone response to exercise that was normalised by 3 weeks of infusion therapy. Basal and post-prandial levels of intermediary metabolites, catecholamines and glucagon were comparable on the two insulin regimens. Responses during exercise were generally similar and no different from those of normal subjects, with the exception of plasma NEFA levels which became abnormally suppressed. Good metabolic control of diabetes is thus accompanied by nearly normal hormonal and metabolic response to moderately severe exercise.

Adult↗
PubMed1983

Epidemiological study of prevalence of chlorpropamide alcohol flushing in insulin dependent diabetics, non-insulin dependent diabetics, and non-diabetics.

An epidemiological study was carried out to compare the prevalence of facial flushing in non-diabetics, patients with insulin dependent diabetes, and patients with non-insulin dependent diabetes in response to 40 ml sherry taken 12 hours after 250 mg chlorpropamide or placebo, administered double blind in randomised order. A flush after chlorpropamide but not placebo was reported by 6.2% of non-diabetics (17/273), 9.7% of insulin-dependent diabetics (14/145), and 10.5% of non-insulin dependent diabetics (25/239), excluding those receiving long term chlorpropamide treatment. The differences were not significant. This response was unrelated to age, sex, body mass index, and family history of diabetes in all three groups. Patients taking long term chlorpropamide, however, showed a significantly (p less than 0.01) higher prevalence of flushing after both chlorpropamide and placebo (56.3%; 9/16) compared with the rest of the non-insulin dependent diabetics (16.7%; 40/239), the insulin dependent diabetics (6.9%; 10/145), and the non-diabetics (5.9%; 16/273). Patients receiving long term chlorpropamide would be expected to flush with sherry after a placebo tablet because of therapeutic plasma concentrations of the drug. It is concluded that there is no evidence of an increased prevalence of chlorpropamide alcohol flushing in response to the single challenge test in non-insulin dependent diabetics compared with insulin dependent diabetics and non-diabetics except in selected patients taking chlorpropamide long term. This study does not support the hypothesis that the chlorpropamide alcohol flush is a specific marker for a subtype of non-insulin dependent diabetes.

Adult↗
PubMed1983

Severe diabetic microangiopathy with normal glucose tolerance and pituitary infarction.

Blood glucose concentrations in a woman with severe retinopathy, nephropathy, and neuropathy were found to be within the normal range. A high random blood glucose concentration was recorded only once, six months before her initial presentation. At necropsy the anterior lobe of the pituitary gland showed old, extensive infarction. Occult pituitary hypofunction may explain severe diabetic microangiopathy in patients with normal glucose tolerance.

Adult↗
PubMed1983

Mortality from coronary heart disease and stroke in relation to degree of glycaemia: the Whitehall study.

In the Whitehall study of 18 403 male civil servants aged 40-64 years the 10 year mortality rates from coronary heart disease and stroke showed a non-linear relation to two hour blood glucose values, with a significantly increased risk for glucose intolerant subjects with concentrations above the 95th centile point (5.4-11.0 mmol/l; 96-199 mg/100 ml) and for diabetics (blood glucose greater than or equal to 11.1 mmol/l; greater than or equal to 200 mg/100 ml). Multiple logistic analysis showed that between one half and three quarters of the relative risks for deaths from coronary heart disease and stroke were "unexplained" by between group differences in risk factors such as age, blood pressure, obesity, smoking, cholesterol concentration, and electrocardiographic abnormalities. Within the glucose intolerant and diabetic groups the risk factors most strongly related to subsequent death from coronary heart disease were age and blood pressure, with less consistent relations for smoking, cholesterol concentration, and obesity. This study confirms the importance of hypertension as a cardiovascular risk factor in groups with glucose intolerance and diabetes, and this may have important preventive implications.

Adult↗
PubMed1983

Maturity onset diabetes of the young is not linked to the insulin gene.

Maturity onset diabetes of the young is inherited as an autosomal dominant condition. Two families with the disease were studied to determine whether the inheritance of this type of diabetes was linked to the insulin gene. A cloned insulin gene probe was hybridised to DNA from the family members and the insulin gene on each chromosome identified by a different fragment length polymorphism. The results showed no linkage between the insulin gene and the inheritance of maturity onset diabetes of the young.

Adolescent↗
PubMed1983

Long term correction of hyperglycaemia and progression of renal failure in insulin dependent diabetes.

The effect of long term correction of hyperglycaemia on the rate of deterioration of renal function was studied in six insulin dependent diabetics with proteinuria due to diabetic nephropathy. After a planned run in observation period of 10 to 24 months patients entered a programme of continuous subcutaneous insulin infusion for up to 24 months. Glycaemic control was promptly and significantly improved and optimal glycaemic values sustained throughout the study. Blood pressure was maintained stable. A control group of six nephropathic diabetics was studied receiving conventional insulin injection treatment but also with blood pressure control over the same period.Despite greatly improved metabolic control in the infusion treated group no significant change in the rate of decline of glomerular filtration rate could be shown, the plasma creatinine concentrations continued to increase, and the fractional clearance of albumin and IgG rose progressively, indicating progression of glomerular damage. The conventionally treated control group behaved similarly. In a single patient receiving the continuous infusion the rate of decline of the glomerular filtration rate slowed considerably, suggesting that the response to strict diabetic control may differ in some patients.These findings suggest that by the time glomerular function has started to fail in diabetic nephropathy the process culminating in end stage renal failure has become self perpetuating and is little influenced by the degree of metabolic control. A new definition of potential clinical diabetic nephropathy is proposed that will permit identification of patients at risk and earlier intervention by glycaemic correction in an attempt to arrest diabetic renal disease.

Adult↗
PubMed1983

Subcutaneous aprotinin causes local hyperaemia. A possible mechanism by which aprotinin improves control in some diabetic patients.

Local changes in blood flow at the subcutaneous injection site of the proteinase inhibitor aprotinin and its diluent were measured by photoelectric plethysmography. Aprotinin, but not its diluent, caused local hyperaemia in five normal subjects and in five stable and five brittle insulin-dependent diabetic patients, local blood flow increasing by 80%-180%. The duration of the hyperaemic response was shorter in the brittle diabetic patients than in the other two groups, but there was wide individual variation. Aprotinin is known to enhance subcutaneous insulin absorption in normal subjects and in some brittle diabetic patients. The basis for this might be through increasing blood flow near the injection site rather than by inhibition of insulin breakdown.

Adult↗
PubMed1983

Monitoring glomerular function in diabetic nephropathy. A prospective study.

Glomerular function was monitored prospectively in 13 patients with insulin-dependent diabetes and diabetic nephropathy for up to 51 months. Glomerular filtration rate, measured by 51Cr-EDTA clearance, showed a linear decline in all patients. Rates of fall ranged between 0.63 and 2.4 ml/minute per month (mean +/- SEM 1.2 +/- 0.16). Plasma creatinine concentration proved to be an insensitive marker of glomerular function, especially in the early phase of nephropathy. A good correlation was found between the rate of change of 51Cr-EDTA glomerular filtration rate and that of inverse creatinine levels when plasma creatinine concentrations exceeded 200 mumol/liter. Inverse plasma beta 2-microglobulin concentrations, however, showed a highly significant correlation (r = 0.93; p less than 0.001) with 51Cr-EDTA glomerular filtration rate over the whole range of values, making it sensitive in screening for early impairment of renal function. A significant relationship (r = 0.85; p less than 0.01) was found between the rates of change of the 51Cr-EDTA glomerular filtration rate and of inverse beta 2-microglobulin levels for plasma beta 2-microglobulin concentrations above 3 mg/liter. A progressive increase in the fractional clearance of albumin, IgG, and beta 2-microglobulin was noted as the glomerular filtration rate fell, indicating an evolving defect in the renal handling of proteins. The rate of decline of the glomerular filtration rate was unrelated to age, sex, duration of diabetes, duration of diabetes before onset of proteinuria, glomerular filtration rate, initial albumin clearance, blood glucose control, and arterial pressure, when diastolic values were below 100 mm Hg. The effect of therapeutic intervention (e.g., blood glucose, blood pressure, or diet) on the progression of diabetic nephropathy can be reliably evaluated by precise measures of rate of decline of glomerular filtration rate and changes in fractional clearance of plasma proteins. The factor(s) determining the individual rate of decline of renal function still remain obscure.

Adult↗
PubMed1983

Hemodynamic factors in the genesis of diabetic microangiopathy.

There are many candidate mechanisms to explain the phenomenon of delayed microvascular disease in the diabetic. All may play some part in determining the genesis, the evolution or the ultimate degree and form of the angiopathy. General metabolic and humoral factors may provide the pathogenetic background against which special local conditions, e.g., in the retina or renal cortex, will determine the morphology of the angiopathy and its functional and structural consequences. Some of the processes occurring in the diabetic person may, however, be of major importance in initiating and maintaining conditions for the evolution of microvascular disease. The hemodynamic changes and the vascular responses to them that we have described are, we suggest, very likely to be an important component of this sort. Unlike the later structural changes, these hemodynamic phenomena are to be found very early in the diabetic state. Of most clinical importance, perhaps, is that they appear, with the achievement of adequate metabolic correction, to be reversible.

Animals↗
PubMed1983

A new miniature, open-loop, extracorporeal insulin infusion pump.

This extracorporeal insulin infuser has been designed to be compact, simple to operate, and suitable either for clinical investigations of insulin-dependent diabetes mellitus or for long term treatment of the condition. A syringe driver of unconventional design is used, and the syringe will be available prefilled with insulin, specially formulated at standard strength for long term infusion. The device is electronically controlled to give variable rates of basal infusion, preset by switch and supplemented by bolus infusions demanded by pushbutton prior to meals. Sufficient insulin is carried in the syringe to meet the needs of most diabetics for at least a week without refilling, and the battery life is commensurately long. Signalling of the mealtime dose regime, and of alarm and failure conditions is by audible means. Insulin will most commonly be delivered subcutaneously, though other routes are possible.

Biomedical Engineering↗