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Biomedical subjects

D J Chisholm

Publications and source records attributed to D J Chisholm.

136 records · Page 8Linked to original sources
PubMedDate not supplied

Pathogenesis of the insulin resistance syndrome (syndrome X).

1. Insulin resistance is an early and major feature in the development of non-insulin-dependent diabetes mellitus (NIDDM), but it is also associated with hyperlipidaemia, hypertension, obesity and cardiovascular disease, the so-called 'insulin-resistance syndrome' (Syndrome X). 2. There is a strong genetic determination of NIDDM and insulin resistance, but the environmental factors of calorie excess, reduced activity and obesity also make a major contribution. 3. Central (abdominal) obesity is much more strongly associated with insulin resistance than is overall obesity. From twin studies, there appears to be specific genetic determinants of central abdominal fat, independent of overall obesity. 4. Calorie restriction and weight loss improve insulin sensitivity in overweight humans. Isocaloric alteration of macronutrients substantially affects insulin sensitivity in rats but not, at least in the short-term, in humans. 5. Exercise training improves insulin sensitivity via increased oxidative enzymes, glucose transporters (GLUT4) and capillarity in muscle as well as by reducing abdominal fat. 6. Metformin has been the only available drug that has been used clinically to significantly improve insulin sensitivity, but the new 'glitazones' (thiazolidinediones) have a more specific effect via altered lipid metabolism.

Animals↗
PubMedDate not supplied

Intensive education improves knowledge, compliance, and foot problems in type 2 diabetes.

Despite the established role of foot care education in diabetes management, reports evaluating such interventions are rare. The effectiveness of an intensive foot care intervention programme and a conventional one were therefore compared in Type 2 diabetes. The intensive group showed significantly greater improvements than the conventional group in foot care knowledge (p less than 0.001), compliance with the recommended foot care routine (p = 0.012), and compliance with the initial advice to consult a podiatrist (other than the project podiatrist) for further treatment (p = 0.008). At the first follow-up visit the intensive group also showed a significantly greater reduction in the number of foot problems requiring treatment than the conventional group.

Diabetes Mellitus, Type 2↗
PubMedDate not supplied

Pharmacokinetics of insulin. Implications for continuous subcutaneous insulin infusion therapy.

This review considers subcutaneous insulin pharmacokinetics, with emphasis on those aspects relevant to subcutaneous insulin infusion devices. These devices are in increasing use for diabetes therapy, although reliable data on subcutaneous insulin absorption is required to optimise their programming. Techniques for obtaining and interpreting pharmacokinetic data are considered. Recent studies would suggest that it is possible to simulate the major physiological fluctuations in blood insulin levels via continuous subcutaneous insulin infusion, combined with appropriate bolus insulin delivery. Most insulin infused subcutaneously will reach the systemic circulation, and in the majority of diabetics, subcutaneous insulin degradation is low. However, the absorption rate is slow and it may take 6 to 8 hours to reach a steady-state following a change in the subcutaneous infusion rate. Thus there is little to be gained from hour by hour adjustments to the basal insulin infusion rate. Basal rate supplementation, and meal insulin requirements, are best met by bolus delivery. It is particularly important to provide increased systemic delivery of insulin with the start of a meal. The most appropriate adjustment for additional exercise may be a small reduction in the preceding meal bolus, rather than a reduction in the basal rate. Studies of the pharmacokinetics of insulin are an important contributing factor to the optimisation of subcutaneous insulin infusion therapy.

Absorption↗
PubMedDate not supplied

Programming of insulin delivery with meals during subcutaneous insulin infusion.

The serum insulin elevation after subcutaneous (s.c.) infusion of 10 U of neutral regular insulin given over 5 or 30 min has been examined in normal subjects to find a delivery profile that would simulate the normal serum insulin response to a meal. Endogenous insulin release, assessed by measurement of C-peptide, was suppressed by an i.v. infusion of 1 U/h neutral regular insulin, beginning 60 min before the s.c. administration and continuing throughout the study. The increment in serum insulin levels after the 5-min s.c. infusion reached a peak of 62 +/- 9.5 mU/L at 45 min, and the rate of elevation of insulin levels closely approximated the normal insulin response to a 50-g, 500 kcal mixed meal. The increment in serum insulin levels with the 30-min s.c. infusion reached a peak of 41 +/- 1.4 mU/L at 75 min. The incremental insulin response up to 180 min (area under the curve) after the 5-min s.c. infusion was 30% greater than the response to the 30-min infusion. On the basis of these studies, we conclude that insulin delivery for meals during s.c. insulin infusion need not be initiated before the meal, but should be given over a period of approximately 5 min or less. Further study is required to delineate the effects of concentration, local degradation, and rate of delivery on entry of s.c. insulin to the vascular system.

Adult↗
PubMedDate not supplied

Comparison of plateau insulin levels achieved by intravenous or subcutaneous insulin infusion: evidence for low rates of subcutaneous degradation.

Continuous insulin infusion via the subcutaneous (s.c.) route is attractive for diabetes therapy because of its simplicity compared with other routes. Some insulin will be degraded locally before systemic absorption, although the magnitude of this degradation has not been established. We have performed in five normal subjects s.c. and intravenous (i.v.) insulin infusions (2.4 U/h) of sufficient duration to compare steady-state systemic appearance rates of exogenous insulin. A steady state was produced after 60-90 min (i.v.) and 6-8 h (s.c.). Blood glucose fell to approximately 2.7 mmol/L in both studies and a fall in C-peptide indicated suppression of endogenous insulin secretion. Plateau insulin levels attributable to systemic entry of exogenous insulin were 36 +/- 2.0 mU/L (i.v. route) and 29 +/- 1.8 mU/L (s.c. route). These indicate a rate of 2.c. degradation of insulin of 19 +/- 5% in the steady state. We conclude that there is a low rate of degradation of insulin during continuous s.c. infusion.

Adult↗
PubMedDate not supplied

Blood glucose control by intermittent loop closure in the basal mode: computer simulation studies with a diabetic model.

A semiclosed loop, bedside insulin infusion system using a simple basal infusion algorithm consisting of a linear transition between two insulin delivery rates as blood glucose (BG) increases has been developed. A theoretical study using computer simulation has now been undertaken to examine the effect of BG sampling frequency and algorithm parameters on BG control. A model for BG control by exogenous insulin in the individual with diabetes was developed from a model for healthy subjects and from clinical data in the literature. Results of computer simulation using this model showed a decrease in BG stability as the sampling interval increased from 1 to 4 h. Simulations also showed a decrease in BG stability as the sensitivity of the control algorithm increased. Choice of an appropriate basal control algorithm involved a compromise between stability, sampling interval, and metabolic control. We conclude that satisfactory metabolic control can be obtained using intermittent BG sampling in the basal state; sampling at intervals of 3 h combined with a basal control algorithm whereby insulin delivery rate increases linearly from 0.5 to 2.5 U/h over the BG range 2-12 mmol/L appears suitable for most diabetic persons. Three-hour sampling offers a good compromise between degree of metabolic control and clinical effort involved.

Blood Glucose↗
PubMedDate not supplied

Insulin dosage reduction. Evaluation of an education-stabilization programme for patients with insulin-dependent diabetes.

A retrospective survey was conducted of 52 consecutive subjects with insulin-treated diabetes who were attending an education-stabilization programme. Eleven subjects (21%) achieved more than a 20% reduction in daily insulin dosage six months after completion of the programme. Compared with the remainder of the group, these subjects had a significantly earlier age of onset, higher initial insulin dosage (mean, 61 units/day, compared with 39 units/day), higher initial insulin carbohydrate and fat consumption, but similar initial glycosylated haemoglobin levels. These results suggest that overinsulinization is a relatively frequent occurrence and should be particularly considered in younger patients who are receiving relatively large doses of insulin.

Age Factors↗
PubMedDate not supplied

A semi-closed loop computer-assisted insulin infusion system. Hospital use for control of diabetes in patients.

Closed loop insulin delivery systems are impractical for widespread hospital use. Thus, a semi-closed loop computer-assisted insulin infusion system (CAIIS) was developed for the intravenous delivery of insulin. In its basal program, insulin delivery is determined by blood glucose measurements at intervals of three hours, while the open-loop meal program delivers 7.5 units over three hours. Control of meal-induced hyperglycaemia was satisfactory in six subjects with diabetes tested over two to four days, as was mean glycaemic control in the four non-obese subjects (7.1 +/- 0.8 mmol/L). To allow for variations in insulin sensitivity, an adjustment incrementing or decrementing the basal insulin delivery rate was applied according to the progressive blood glucose response. Empirical use of this adjustment resulted in good control (mean blood glucose level, 4.1-7.5 mmol/L) in 10 additional subjects with diabetes. This study demonstrates the potential usefulness of a semi-closed loop insulin infusion system.

Adult↗