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Biomedical subjects

J C Pickup

Publications and source records attributed to J C Pickup.

At least 91 records · Page 5Linked to original sources

Correction of exercise-induced microalbuminuria in insulin-dependent diabetics after 3 weeks of subcutaneous insulin infusion.

The effect of metabolic near-normalization, induced by continuous subcutaneous insulin infusion, on the exaggerated microalbuminuria of exercise was studied in eight insulin-dependent diabetic men selected for normal resting albuminuria. Patients were studied in randomized order during the ordinary glycemic control of conventional insulin treatment (CIT) and after 3 wk of "super-control" with continuous subcutaneous insulin infusion (CSII). Seven age-matched healthy men were used as controls. In the diabetics the albuminuric response to fixed-load bicycle exercise (600 kpm/min for 20 min) during CIT greatly exceeded that of the normal controls (P less than 0.01). After 3 wk of optimal plasma glucose control, urinary albumin excretion rates in response to the same exercise load were significantly reduced (P less than 0.02) in the diabetics and became statistically indistinguishable from that of the normal controls. The urinary excretion rate of beta 2-microglobulin, an index of tubular function, was not increased significantly by exercise either during CIT or CSII. The plasma glucose fall after exercise was greater (P greater than 0.001) on CIT (8.5 +/- 0.9 mmol/L) than on CSII (4.0 +/- 0.6 mmol/L). The pulse rate acceleration in response to exercise was significantly reduced after 3 wk of CSII (P less than 0.05). The exercise-induced systolic blood pressure rise was similar in controls and diabetics on both therapeutic regimens. Thus, a period of metabolic near-normalization in the diabetic corrects the abnormal transglomerular passage of albumin induced by moderately strenuous muscular exercise and reduces the exercise tachycardia. Improved control with CSII appears to reduce greatly the risk of exercise-induced hypoglycemia, despite much tighter glycemic control.

Adult↗

Human insulin produced by recombinant DNA technology: safety and hypoglycaemic potency in healthy men.

Human insulin synthesised by recombinant DNA technology was compared with highly purified porcine insulin in healthy men. Intracutaneous injection over a wide range of concentrations of both insulins into five subjects gave rise to no local reactions over a 48 h period. The glycaemic response to standard subcutaneous injection at high and low dose levels was measured with both insulins in each of six men. Plasma glucose decrement with the two insulins was similar but human insulin was perhaps slightly more potent than porcine insulin at the low dose, and slightly less so at the high. The glycaemic response to the isulins, each infused intravenously at high and low concentrations for 1 h in a further six subjects, showed a similar trend. Depression of glycaemia with human insulin slightly exceeded that with porcine insulin at the low concentration infusion and fell slightly short of it at the high. Genetically synthesised human insulin seems to be safe and effective in man. Its dose-response relationship may differ from that of porcine insulin.

Adult↗

Long-term continuous subcutaneous insulin infusion in diabetics at home.

6 insulin-requiring diabetics were treated at home with continuous, long-term, dual-rate subcutaneous insulin infusion (CSII) by means of a portable syringe pump. The duration of infusion was 48--111 days. Patients were initially stabilised on CSII in hospital and then allowed home, where capillary-blood glucose control was monitored by the patients with glucose-oxidase reagent strips. Patients diluted and changed their own insulin for the pump, adjusting the dose according to the control achieved. Mean (+/- SD) blood-glucose values ranged from 4.8 +/- 1.6 to 7.5 +/- 1.6 mmol/l. In 1 longstanding diabetic insulin requirements fell from 92 U/day to about 35 U/day on CSII. 2 newly diagnosed juvenile-onset diabetics were also infused: in 1 patient requirements fell to zero after 48 days and in the other the dose fell to 14 J/day after 51 days of CSII. No cannula-site infection or significant palpable lipodystrophy was experienced. Patients treated with "open-loop" systems have little or no insulin reserve: potential loss of control--for example, during intercurrent illness-demands careful metabolic monitoring and prompt correction.

Adolescent↗

Continuous subcutaneous insulin infusion: improved blood-glucose and intermediary-metabolite control in diabetics.

Blood-levels of glucose and the major intermediary metabolites, lactate, pyruvate, 3-hydroxybutyrate, and alanine, were measured in 7 insulin-dependent diabetics during 24 h of continuous subcutaneous insulin infusion (C.S.I.I.) from a portable dual-rate syringe pump. Results were compared with metabolic profiles during the patients' conventional insulin treatment and with those of 17 non-diabetics. The mean 24 h plasma-glucose during C.S.I.I. was not significantly different from that in non-diabetics. During infusion blood concentrations of lactate, pyruvate, 3-hydroxybutyrate, and alanine were also close to those in the non-diabetic state. Thus, C.S.I.I. provides strict control not only of blood-glucose but also of major metabolites, an essential prerequisite for investigating the influence of good metabolic control on diabetic microangiography.

Adolescent↗

Effect of control of blood glucose on urinary excretion of albumin and beta2 microglobulin in insulin-dependent diabetes.

To study the effects of improved control of blood glucose on markers of renal glomerular and tubular function, we initially determined, by radioimmunoassay technics, urinary excretion rates of albumin and beta2 microglobulin in 17 nondiabetic subjects and in 43 insulin-dependent, clinically nonproteinuric diabetic patients. Duration of diabetes ranged from six months to 39 years, and the patients were studied while receiving conventional therapy. Mean urinary albumin excretion was significantly elevated in the diabetics, but beta2-microglobulin excretion rates were not different from those of the controls, suggesting that the increased albumin excretion was due to increased transglomerular loss of albumin. Seven patients with long-term diabetes (duration of six to 33 years), selected because of elevated albumin excretion, were studied before and during a continuous, subcutaneous insulin infusion for a period of one to three days. Urinary albumin excretion was significantly reduced during the insulin infusion, but mean beta2-microglobulin excretion did not change. Strict control of blood glucose, even in the short term, may reverse a functional renal abnormality in long-duration, insulin-dependent diabetes.

Adult↗

Continuous subcutaneous insulin infusion:good blood glucose control for up to 4 days.

Six insulin-dependent diabetics were studied on their conventional insulin treatment and during continuous, dual-rate, subcutaneous insulin infusion for periods of up to 4 days. Dabetic control, as assessed by mean plasma glucose, range of plasma glucose values, M-value or range of M-values was improved significantly in 5 patients (mean +/- SD plasma glucose concentration on final infusion day 6.9 +/- 1.3 mmol/l, versus 11.3 +/- 3.2 mmol/l on conventional treatment). Once a suitable insulin dose was established blood glucose control could be maintained by continuous subcutaneous insulin infusion using the same daily infusion rate without frequent adjustment. In some case this was less than the daily dose on the conventional treatment. However, glycaemic control in one "brittle" diabetic, with unpredictable swings in blood glucose on her normal regimen, was not improved by continuous subcutaneous insulin infusion. During the period tested there was no sepsis at the cannula implantation site and patients did not find the system uncomfortable or unduly inconvenient.

Adult↗

Clinical application of pre-programmed insulin infusion: continuous subcutaneous insulin therapy with a portable infusion system.

Strict control of blood glucose was achieved by continuous subcutaneous insulin infusion with a specially adapted Mill Hill Infuser for 3-4 days. This led to normalisation of some of the intermediary metabolites. In a few patients, subcutaneous infusions have been carried out for periods up to 3 months with home monitoring of blood glucose, without infection or lipodystrophy. Short-term improvement of metabolic control was associated with recovery of abnormal renal glomerular permeability to albumin.

Alanine↗

Technology of pre-programmable insulin delivery systems: continuous subcutaneous insulin infusion.

Dual-rate continuous subcutaneous insulin infusion was performed with a specially adapted Mill Hill Infuser. The infuser delivers 2 rates, a slow rate of ca. 50 microliter/h and an eightfold higher rate, designed to cover the increased requirement during meals. The high rate is engaged by pressing a button on the side of the pump, and returns automatically to the basal level after 17 min. Insulin is delivered to the subcutaneous side by a nylon cannula.

Blood Glucose↗