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Biomedical subjects

H Keen

Publications and source records attributed to H Keen.

At least 109 records · Page 6Linked to original sources
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

Limitations and problems of diabetes classification from an epidemiological point of view.

There are residual ambiguities between the two main current glycaemic definitions of the categories of DM, IGT and normal GT which should be resolved. IGT is clearly a highly heterogeneous category and could with advantage be resolved into its identifiable subsets though adequate data for this is not yet available. The concept of insulin dependency requires clearer definition for operational purposes. Biochemical parameters (e.g. C-peptide responses) may help. Attempts to combine clinical manifestations and pathogenic mechanisms in a single classification (e.g. IDDM/NIDD versus Type I/Type II) should be handled with care. If the term Type I is to be retained, it should be applied to a defined pathogenic process, not to a clinical type of DM. The term Type II is inadequately defined at present. IDDM and NIDDM, clinical descriptive terms, may be provoked by a variety of pathogenic mechanisms (i.e. they are 'heterogeneous'). They could be subclassified by mechanism (when known). More visibility should be given in classification to non-Europid forms of DM (e.g. 'Tropical or 'Nutritional' DM). A staging dimension should be recognised in classifications of DM. Future classifications will benefit from the incorporation of the presence or absence of susceptibility/resistance factors to diabetes itself or to its severe long term sequelae. There remain uncertainties about the definitions and clinical implications of gestational DM (and gestational IGT) not discussed above. It should be accepted that different user groups may need different subclassification of diabetes and glucose intolerance to meet their specific requirements and so long as this is made clear and definitions are adequate this should not be a problem. However, for the present, all groups should accept the proposed glycaemic definitions of DM or IGT for the purposes of comparability.

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↗
PubMed1985

Continuous subcutaneous insulin infusion does not induce a significant acute phase response of serum amyloid A protein.

In a study of 23 matched pairs of Type 1 (insulin-dependent) diabetic patients receiving continuous subcutaneous insulin infusion or conventional insulin injection therapy respectively, there were no significant differences in serum levels of the acute phase proteins, serum amyloid A and C-reactive protein. These results do not support the suggestion that continuous subcutaneous insulin infusion stimulates serum amyloid A production or that it carries a risk of inducing reactive systemic amyloidosis.

Adolescent↗
PubMed1985

Frequency of diabetic ketoacidosis and hypoglycemic coma during treatment with continuous subcutaneous insulin infusion. Audit of medical care.

The frequency of diabetic ketoacidosis and hypoglycemic coma in a large series of patients with insulin-dependent diabetes treated by long-term continuous subcutaneous insulin infusion was compared with the frequency of these events in a matched group of patients treated by conventional insulin injections at the same hospital over the same period of time. Ketoacidosis and hypoglycemic coma occurred no more frequently in continuous subcutaneous insulin infusion-treated patients. Therefore, intensified insulin therapy achieved by continuous subcutaneous insulin infusion does not appear to be associated with a greater risk of ketoacidosis or hypoglycemic coma than does conventional insulin therapy.

Adult↗
PubMed1985

Conference on insulin pump therapy in diabetes. Multicenter study of effect on microvascular disease. Origin and design of the Kroc Collaborative Study.

Although the benefits of metabolic intervention on the microvascular complications of diabetes mellitus remain unproven, it is generally assumed though not proven that prognosis in terms of blindness and renal failure will reflect the long-term glycemic response to therapy. Treatment goals however remain poorly defined. Costs and hazards of achieving near-normoglycemia in insulin-dependent diabetes mellitus (IDDM) are major. A multicenter trial was proposed to test the hypothesis that in IDDM two levels of mean glycemia, sufficiently separated to examine the control/complications relationship, could be maintained by the six collaborating centers, using randomized patient allocation to conventional insulin therapy (CIT) and continuous subcutaneous insulin infusion (CSII) as the alternative treatment modalities. Methods of maintaining and monitoring metabolic control and of assessing renal and retinal responses were to be applied, evaluated, and possibly improved. All clinics shared a common experimental protocol, which received ethical approval at each treatment center. Retinal assessment facilities were provided by the Fundus Photograph Reading Center at the University of Wisconsin in Madison, and at the Diabetic Retinopathy Department, Royal Postgraduate Medical School, Hammersmith, United Kingdom. The Central Biochemistry Laboratory was at the University of Newcastle, United Kingdom. Collaborators agreed on policy for recruitment, baseline assessment, and randomization of patients with IDDM, complicated by early microvascular disease. CIT took the form of the unchanged prestudy regimen; glycemic goals were set for CSII and their achievement based on inpatient and outpatient sampling of plasma glucose. Glycosylated hemoglobin was measured, retinal abnormalities recorded photographically, and urinary albumin excretion quantitated at baseline, 4, and 8 mo in all patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical Trials as Topic↗
PubMed1985

Eight-month correction of hyperglycemia in insulin-dependent diabetes mellitus is associated with a significant and sustained reduction of urinary albumin excretion rates in patients with microalbuminuria.

Persistent Albustix-positive proteinuria and subsequent chronic renal failure are frequently encountered in insulin-dependent diabetes mellitus (IDDM). Rates of decline of renal function may be modified by treatment of accompanying hypertension, but studies of the effects of long-term continuous subcutaneous insulin infusion (CSII) on deterioration of renal function provide no statistically significant evidence of benefit of near-normoglycemia. However, short-term studies in IDDM subjects with negative Albustix tests but subclinically raised levels of albumin excretion rate (AER) have shown that treatment with CSII significantly reduces this microalbuminuria. The prospective, controlled 8-mo Kroc Collaborative Study therefore offered the opportunity of examining more protracted effects of CSII-induced metabolic correction upon microalbuminuria. Twenty-four-hour urine collections obtained at baseline, 4, and 8 mo were available from 59 Albustix-negative patients. Beta 2-microglobulin excretion was normal. The 39 normoalbuminuric (AER less than 12 micrograms/min) patients did not differ from the 20 microalbuminuric (AER elevated between 13.2 and 192.6 micrograms/min) with respect to distributions of age, sex, and duration of diabetes. In both the normoalbuminuric and the microalbuminuric groups studied at 4 and 8 mo, percent glycosylated hemoglobin (%HbA1) and mean blood glucose were significantly decreased during CSII compared with baseline values, whereas no change occurred in the group continuing their conventional insulin therapy (CIT). AER did not differ between CIT and CSII treatments in the normoalbuminuric group. AER fell significantly in the CSII-treated microalbuminuric patients at 4 (P less than 0.05) and 8 (P less than 0.01) mo but showed no consistent change in the CIT microalbuminuric group.(ABSTRACT TRUNCATED AT 250 WORDS)

Albuminuria↗
PubMed1984

Glycaemic control in diabetic nephropathy.

To investigate the quality of glycaemic control that is achievable in diabetic patients with persistent proteinuria and asymptomatic but declining renal function three matched groups of patients were studied. The first comprised diabetics with proteinuria receiving continuous subcutaneous insulin infusion; the second, diabetics without proteinuria receiving continuous subcutaneous insulin infusion; and the third, diabetics with proteinuria receiving conventional insulin treatment. Glycaemic control in patients receiving continuous subcutaneous insulin infusion was shown to be appreciably worse during the daytime in diabetics with proteinuria than in diabetics without proteinuria, although greatly superior to that in diabetics with proteinuria receiving conventional insulin treatment. The loss of glycaemic control in patients with proteinuria receiving continuous subcutaneous insulin infusion probably occurred as a response to daytime hypoglycaemia and a consequent reduction in the proportion of the total insulin dose given prandially. Difficulty in controlling blood glucose concentrations may be a factor in the failure of intensified insulin regimens to influence the progression of diabetic renal disease.

Adult↗
PubMed1984

Glycaemia, arterial pressure and micro-albuminuria in type 1 (insulin-dependent) diabetes mellitus.

Plasma glucose control and arterial pressure were assessed in 28 Type 1 (insulin-dependent) diabetic patients with different degrees of micro-albuminuria. They were divided into two groups according to their urinary albumin excretion rate: a low micro-albuminuria group (n = 16) with albumin excretion ranging between 12.1 and 28.9 micrograms/min and a high micro-albuminuria group (n = 12) with albumin excretion between 32.4 and 91.3 micrograms/min. The groups were matched for age, sex and duration of diabetes with the same number of normo-albuminuric (2.0-10.4 micrograms/min) diabetic control subjects. Both the low and high micro-albuminuria groups had significantly higher glycosylated haemoglobin levels and mean plasma glucose concentrations during a 24-h profile than their respective normo-albuminuric control subjects. A correlation between glycosylated haemoglobin level and urinary albumin excretion rate was found in the whole study group (r = 0.48; p less than 0.001). Arterial pressure (both systolic and diastolic) was significantly higher in the high micro-albuminuria group than in either the control group or the low micro-albuminuria group. A significant correlation was found between arterial pressure and albumin excretion rate in the whole study population (r = 0.49; p less than 0.001) as well as in the pooled micro-albuminuria groups (r = 0.43; p less than 0.05). Multiple regression analysis showed that glycosylated haemoglobin and arterial pressure levels were independently correlated with albumin excretion rates. Diabetic patients with micro-albuminuria of any degree have worse glycaemic control than normo-albuminuric patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1984

Plasma renin activity in insulin-dependent diabetics with raised glomerular filtration rate.

Basal and ambulant plasma renin activity (PRA) were measured in 12 insulin-dependent diabetics (IDDS) with elevated glomerular filtration rate (GFR), 12 IDDs with normal GFR matched for age, sex and duration of diabetes and 12 age and sex matched non-diabetic control subjects. The two diabetic groups did not differ with respect to extracellular fluid volume, urinary sodium excretion, arterial blood pressure, mean plasma glucose concentration or urinary glucose excretion. Basal PRA did not differ significantly between the three groups. Ambulant PRA was significantly higher (P less than 0.02) in the group of IDDs with elevated GFR than in the control group. Our data suggest that, in IDDs with high GFR, haemodynamic alterations may stimulate a rise in PRA and thus angiotensin, a potent vasoconstrictor. Whether this represents an attempt of the renin-angiotensin system to normalise GFR or is the result of insensitivity of the renal vasculature to circulating angiotensin remains to be established.

Adolescent↗
PubMed1984

Prostaglandin E1 accelerates subcutaneous insulin absorption in insulin-dependent diabetic patients.

The powerful vasodilator, prostaglandin E1 (PGE1), was added to Actrapid insulin to try to accelerate the early phase of subcutaneous insulin absorption through increasing injection site blood flow. Actrapid insulin alone (6U) and insulin containing PGE1 (7.5 X 10(-6) M) were injected on different days into 13 fasting insulin-dependent diabetics. With the insulin/PGE1 mixture, increases in both free and total plasma insulin concentrations were greater at all times up to 120 minutes after injection than with insulin alone, with significant differences in the first 40 minutes. With insulin/PGE1 the area under the total plasma insulin curve increased significantly more rapidly between 80 and 120 minutes. Plasma glucose concentrations fell consistently more rapidly with insulin/PGE1 than with insulin alone although the differences were small (mean fall +/- S.E.M. at 120 minutes: 4.9 +/- 0.5 mmol/l vs 4.0 +/- 0.6; p = 0.02). Addition of local hyperaemic agents to short-acting insulin preparations could be therapeutically useful in hastening insulin entry to the circulation at mealtimes.

Adolescent↗
PubMed1984

The Whitehall Study: ten year follow-up report on men with impaired glucose tolerance with reference to worsening to diabetes and predictors of death.

Two-hundred and four men with a defined degree of impaired glucose tolerance derived from the Whitehall Survey and its pilot study were enrolled in a therapeutic trial and followed for ten years. For the first five years of the trial approximately half the group received 50 mg phenformin daily and the other half an identical placebo. For the whole ten years of the trial approximately half the group were recommended a diet in which carbohydrate intake was limited to 120 g/day, while the other half was recommended a qualitative limitation of sugar intake. 60 men (29.4%) worsened to diabetes during the follow-up period. The major independent predictor of worsening was the baseline blood glucose level (glucose tolerance). High baseline plasma triglyceride levels and low baseline systolic blood pressure levels were also independent predictors of worsening, though of lower significance (0.01 less than p less than 0.05). Obesity, measured as body mass index, was not a significant risk factor. Thirty-nine men died, with 19 deaths ascribed to coronary heart disease (CHD). Baseline blood pressure significantly predicted both all causes and CHD mortality. All causes mortality rates were higher in the less obese. Allocation to drug or diet therapy did not significantly affect mortality rates or the proportions worsening to diabetes.

Blood Glucose↗
PubMed1984

Urinary insulin excretion rate: an index of free insulinaemia in insulin-dependent diabetics.

In 25 insulin-dependent diabetics, 14 managed by conventional insulin injection treatment (CIT) and 11 treated by continuous subcutaneous insulin infusion (CSII), there was a highly significant correlation between urinary insulin excretion rate (IER) per 1.73 m2 and mean serum free insulin concentration (r = 0.73, p less than 0.001), measured over a 24 h period. Urinary IER and mean daily serum free insulin levels were significantly higher in diabetics than in non-diabetics. CSII-treated patients had significantly lower mean 24 h plasma glucose levels than CIT-treated patients despite similar values of urinary IER and mean daily serum free insulin in the two groups. Urinary IER may be a useful indicator of average insulinaemia in large scale studies, avoiding the problems of multiple blood sampling and immunoassay in the presence of anti-insulin antibodies.

Adult↗