Search PubMed⌕ Search

Biomedical subjects

H Keen

Publications and source records attributed to H Keen.

298 records · Page 17Linked to original sources

Plasma insulin and C-peptide after subcutaneous and intravenous administration of human insulin (recombinant DNA) and purified porcine insulin in healthy men.

We have compared the plasma profiles of C-peptide, human insulin (recombinant DNA), and purified porcine insulin of pancreatic origin (PPI) in six nondiabetic men after low-dose (4.8 U) or high-dose (9.6 U) subcutaneous injection and low-rate (1.0 U/h) or high-rate (1.7 U/h) intravenous infusion. There was no significant difference in plasma C-peptide or glucose levels when human insulin was compared with PPI at either dose level for subcutaneous injection or intravenous infusion. Thus, there was equal suppression of endogenous insulin by the two species of exogenous insulin. For low-dose subcutaneous injection there was no significant difference between plasma insulin levels of the two species at single time points or when areas were compared. For high-dose subcutaneous injection mean plasma insulin levels were higher after human insulin than after PPI (20-300 min); this serial difference reached conventional statistical significance at 50 min (P less than 0.05) and 90 min (P less than 0.01). For the area under plasma insulin profiles between 0 and 90 min after high-dose s.c. injection, human insulin was higher than PPI (P = 0.06). There was no significant difference between insulin concentrations after human insulin and PPI given by either low- or high-dose intravenous infusion, except that high-dose PPI values (55-110 min) were slightly but significantly higher after high-dose intravenous infusion. Further comparisons of the pharmacokinetics of human and other species of insulin are, therefore, justified in larger numbers of subjects and particularly in diabetic individuals.

Animals↗

Meeting the problems of first-generation insulin infusion pumps: clinical trial of a new miniature infuser.

We designed and constructed a new miniature, open-loop insulin infusion pump specifically to overcome the problems of many first generation insulin infusers. Special features are small size, adjustable volumetric basal infusion rate, rapid electronically mediated prandial insulin boosts, facility for doubling and halving the basal infusion rate and/or prandial delivery, and alarms for low battery state, motor over-run, stoppage, and control circuit malfunction. The infuser takes a specially designed syringe prefilled with short-acting insulin, sufficient in most diabetic patients for at least 7 days treatment with 100 U/ml insulin. To test clinical efficacy nine insulin-dependent diabetic patients received continuous subcutaneous insulin infusion (CSII) with the new infuser for periods up to 6 mo. Four patients previously CSII-treated with a first-generation pump and five who were new to CSII achieved and maintained the expected degree of near-normoglycemia. There were no pump breakdowns and a questionnaire completed by patients during the study confirmed ease and simplicity of operation and an appreciation of the advantages of the new pump compared with one widely used first-generation infuser.

Adult↗

Assessment of a new visual blood glucose strip.

A new double-tipped strip for home glucose monitoring without a meter is described. Comparison between values obtained with the new method by trained nursing staff and those obtained with a glucose-oxidase analyzer demonstrates close correlation between the two methods (r = +0.95, a = +22.2 mg/dl, b = +1.14). The mean concentration in 117 strip tests over an analyzer range of 5-775 mg/dl (0.3-43.0 mmol/L) was 52 mg/dl (2.9 mmol/L) greater than the analyzer estimate. Forty-seven percent of samples were read as the color block closest to the analyzer estimate. Samples in the lower glucose range tended to read one block high. The technique is faster to perform than most other visual blood glucose strip methods, and is a useful addition to the equipment available for home glucose monitoring. Modifications to the strip by the manufacturers appear to have overcome the low value over-reading error.

Autoanalysis↗

Continuous intravenous insulin infusion in the management of brittle diabetes: etiologic and therapeutic implications.

Continuous intravenous insulin infusion (CIVII) was used to treat five brittle insulin-dependent diabetic women (aged 16-29 yr) who had failed to achieve satisfactory glycemic control during intensified subcutaneous insulin treatment including continuous subcutaneous insulin infusion (CSII). Insulin was infused through an indwelling central venous catheter by a portable pump for 3-16 mo. During CIVII, only three subjects obtained satisfactory glycemic control and only for short periods. Generally, as with CSII, control was erratic and unpredictable and three subjects intermittently had high insulin requirements (200 U/day). By contrast, three stable insulin-dependent diabetic subjects achieved near-normoglycemia within 1-3 days of starting CIVII with daily insulin dosages of 30-90 U. The lives of all five brittle subjects continued to be disrupted by frequent hospital admissions during CIVII treatment. Deliberate interference with their own treatment (including tampering with pumps and central venous catheters) was thought to be a major contribution to instability in two of the brittle subjects. In the others, the ineffectiveness of CIVII suggests that brittleness was not due solely to defective subcutaneous insulin absorption, as had previously been suggested in other CSII-unresponsive brittle subjects. Although CIVII has reportedly been successful in managing brittle diabetes, the technique may not be useful in all brittle individuals, as illustrated by the poor glycemic responses of these subjects and the serious complications (including local infection, septicemia, and thrombosis) they suffered.

Adolescent↗

Rarity of a marked "dawn phenomenon" in diabetic subjects treated by continuous subcutaneous insulin infusion.

We assessed the quality of overnight glycemic control and the frequency of the "dawn phenomenon" (nadir-0800 h glycemic increase) in 41 insulin-dependent diabetic patients treated by continuous subcutaneous insulin infusion (CSII). Mean plasma glucose levels were near-normal during the 24 h and, in particular, constant throughout the night. In a subset of six patients overnight plasma free insulin concentrations were also constant during CSII. The majority of profiles (88%) showed a glucose nadir from 2.0 to 5.9 mmol/L (most frequently at 0600 h) and had an 0800 h value from 2.0 to 6.9 mmol/L (92%). A large proportion (46%) of profiles showed a zero or negative nadir-0800 h glycemic increase. In 22 patients with three or more profiles recorded at the same basal insulin infusion rate, only one of 103 profiles had a fasting glycemic increase greater than an arbitrary value of 5.0 mmol/L (5.3), although many patients exhibited small dawn glycemic increases (e.g., 14 of 22 had a mean increase of from 0 to 2 mmol/L). In 12 subjects a 15% reduction in basal insulin infusion rate increased the mean +/- SEM dawn glycemic increase from 0.58 +/- 0.25 mmol/L to 2.7 +/- 0.76 mmol/L (P less than 0.025) as well as significantly increasing the nocturnal nadir and 0800 h plasma glucose concentrations. Thus, a marked dawn phenomenon is rare when a single but adequate basal infusion rate is used for CSII, and this questions the need in the majority of patients for preprogrammable pumps with nocturnal infusion rate changes.

Adult↗

Hypoglycemia and counterregulation in insulin-dependent diabetic patients: a comparison of continuous subcutaneous insulin infusion and conventional insulin injection therapy.

Eleven insulin-dependent diabetic patients were treated in random order by 2-mo continuous subcutaneous insulin infusion (CSII) or 2-mo conventional injection treatment (CIT) with crossover to the alternative regimen. Mean plasma glucose concentrations throughout the day were significantly lower during CSII than during CIT, but the percentage of plasma glucose values less than 2.5 mmol/L, obtained from outpatient self-collected diurnal profiles, was similar for both treatments (CSII vs. CIT: 5.9 and 4.8%, respectively). Reported symptomatic hypoglycemia at home was not significantly different in the whole group of patients treated by CSII or CIT but was reduced by a mean of 57% (P less than .02) in the five patients on CSII who experienced frequent symptomatic hypoglycemic episodes (greater than 4/2 mo) during CIT. Neither the plasma glucose concentration at which the patients recognized induced hypoglycemia nor the glycemic or counterregulatory hormone responses for 60 min thereafter were changed by CSII treatment.

Adult↗

Prolonged weight loss with dexfenfluramine treatment in obese patients.

17 patients with refractory obesity, 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 were treated for 24 weeks with dexfenfluramine; average cumulative weight loss after 12 weeks in these patients (5.7 +/- 0.1 kg) was significantly greater than in the patients who had been treated initially with placebo. After 24 weeks of dexfenfluramine treatment there was a further significant increase in cumulative weight loss (7.0 +/- 0.8 kg; p = 0.05). The incidence of side effects in both trials was lower than that reported in previous studies of racemic dlfenfluramine. The clinically significant weight loss, and low incidence of unwanted effects, suggest that dexfenfluramine has a role in the treatment of refractory obesity.

Adult↗